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Introduction: Evidence on the prevalence of foot problems among people with diabetes in India at a national level is lacking. Hence, this study was aimed to assess the burden of high-risk (HR) feet in people with diabetes across India., Research Design and Methods: A cross-sectional national-level project 'Save the Feet and Keep Walking' campaign was conducted by the Research Society for the Study of Diabetes in India (RSSDI) from July 10, 2022 to August 10, 2022. A modified version of 3 min foot examination was used to assess the foot problems. Around 10 000 doctors with RSSDI membership were trained online to conduct foot screening and provided a standardised monofilament for detection of loss of protective sensation. People with diabetes aged >18 years who visited the clinics during the study period were examined for foot problems. Data were collected online using the semi-structured questionnaire. A total of 33 259 participants with complete information were included for the final analysis. The foot at risk was categorised based on International Working Group on the Diabetic Foot guidelines 2023., Results: Nearly 75% of the participants were aged above 45 years. Around 49% had diabetes duration >5 years and uncontrolled diabetes (hemoglobin A1c >8%). Presence of history of foot ulcer (20%), lower limb amputation (15.3%), foot deformities (24.5%) and absence of diminished dorsal pedis and posterior tibial pulses (26.4%) was noted in the study participants. Around 25.2% of them had HR feet and highly prevalent among males. Diabetic kidney and retinal complications were present in 70% and 75.5% of people with HR feet. Presence of heel fissures (OR (95% CI) 4.6 (4.2 to 5.1)) and callus or corns (OR (95% CI) 3.6 (3.3 to 4.0)) were significantly associated with HR feet., Conclusions: One-fourth of people with diabetes were found to have HR feet in India. The findings are suggestive of regular screening of people with diabetes for foot problems and strengthening of primary healthcare., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Over the years, several studies have been conducted by utilizing bibliometric techniques to reveal research trends in various sub-fields of medical sciences, including arthritis research. Although no bibliometric study has been conducted Methods:In this study, we examined the publications of Indian scholars on Rheumatoid Arthritis (RA) in the last three decades, using various quantitative and qualitative bibliometric indicators. The publications on RA (from 1994-2023) in the Scopus database were identified, analysed and evaluated using a pre-defined search strategy, and specialised software., Results: 1603 papers were published on RA research that was cited 36814 times (averaging 11.48 citations per paper or CPP). The 18.65% and 16.71% of India's total publications indicated received external funding. The most productive Indian organizations were AIIMS (New Delhi), SGPGIMS (Lucknow) and PGIMER (Chandigarh). The most impactful organizations were AMU (Aligarh), Fortis Healthcare Ltd. (Gurgaon), and Punjab University (Chandigarh). The most productive authors were A. Aggarwal, R. Misra, A. Chopra, and U. Kumar. The most impactful authors were A. Aggarwal, A. Ghosh, S. Shankar, and R. Misra. Medicine (64.2% share), Pharmacology, Toxicology and Pharmaceutics (22.0% share), Biochemistry, Genetics and Molecular Biology (19.8% share) and Immunology and Microbiology (12.8% share) contributed the most publications in this area. Clinical studies (40.9% share), pathophysiology (13.2% share) and the treatment outcome (9.0% share) accounted maximally. The most significant keywords appearing in the area were: "Rheumatoid Arthritis", "Methotrexate", and "Rheumatoid Factor"., Conclusions: This study provides insight into past, present, and future areas of India on research in RA and will help scholars identify the areas of collaboration.

A barrier to meeting the goal of universal health coverage in India is the inequality in utilisation of health services between indigenous and non-indigenous people. This study aimed to explore the determinants of utilisation, or non-utilisation, of public healthcare services among the Santals, an indigenous community living in West Bengal, India. The study holistically explored the utilisation of public healthcare facilities using a framework that conceptualised service coverage to be dependent on a set of determinants - viz. the nature and severity of the ailment, availability, accessibility (geographical and financial), and acceptability of the healthcare options and decision-making around these further depends on background characteristics of the individual or their family/household. This cross-sectional study adopts ethnographic approach for detailed insight into the issue and interviewed 422 adult members of Santals living in both rural (Bankura) and urban (Howrah) areas of West Bengal for demographic, socio-economic characteristics and healthcare utilisation behaviour using pre-tested data collection schedule. The findings revealed that utilisation of the public healthcare facilities was low, especially in urban areas. Residence in urban areas, being female, having higher education, engaging in salaried occupation and having availability of private allopathic and homoeopathic doctors in the locality had higher odds of not utilising public healthcare services. Issues like misbehaviour from the health personnel, unavailability of medicine, poor quality of care, and high patient load were reported as the major reasons for non-utilisation of public health services. The finding highlights the importance of improving the availability and quality of care of healthcare services for marginalised populations because these communities live in geographically isolated places and have low affordability of private healthcare. The health programme needs to address these issues to improve the utilisation and reduce the inequality in healthcare utilisation, which would be beneficial for all segments of Indian population.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been used for almost a decade and have proven to be effective not only in managing Type 2 diabetes (T2D), but their cardio and renal protective features make them very useful in managing patients with risk of multiple comorbidities. This systematic review was undertaken by the authors because there is no evidence currently available in India that has studied the suitability of SGLT2i as a first-line agent in patients newly diagnosed with T2D in India., Materials and Methods: First, literature was searched to identify features that are considered important when deciding on a first-line agent for managing T2D. A total of 5 broad topics were identified-glycemic control, extra glycemic effects, antihyperglycemic combination therapy, safety, and cost-effectiveness. These domains had further subheadings, and a total of 16 domains were identified. Metformin is the drug of choice as a first-line agent in such situations and has been considered the gold standard for evaluating the effects of SGLT2i across these domains. A systematic literature review on each domain was conducted to compare SGLT2i with the gold standard in Indian patients newly diagnosed with T2D. Evidence was graded (levels of evidence (LoE)-A, B, and C), and recommendations (class of recommendation (CoR)-I, II, and III) were classified by the expert group as defined in the methodology., Results: According to the systematic reviews conducted, 11 domains had Level A evidence, 2 domains (impact on lipids and gut microbiome) had Level B, and 3 domains had Level C (β-cell function, renal protection, and glycemic variability) evidence. Based on evidence and expert opinion, the authors recommend SGLT2i as a first-line agent for managing newly diagnosed patients with T2D with a Class I recommendation for 13 domains and Class II for the remaining 3 (impact on lipids, gut microbiome, and β-cell function). Although a poorer level of evidence (Level C) was available for the glycemic variability domain, the authors still reported this as Class I recommendations according to their expert opinion and consensus., Conclusion: This article advocates adopting SGLT2 inhibitors as the primary treatment choice for treating patients with newly diagnosed T2D in India., (© Journal of the Association of Physicians of India 2023.)

Background and Aims: This study aimed to assess the current status of India's COVID-19 research from the top 100 most cited papers, using bibliometrics methods and indicators and suggest strengths and weaknesses., Methodology: Publications on COVID-19 research from India between December 2019 and 22 August 2023 were retrieved from the Scopus database. From 37101 studies retrieved, the first top 100 Highly Cited Papers (HCPs) having received 270 to 2931 citations, were identified., Results: The top 100 most cited Indian papers were published from 2020 to 2023, with the majority (75) in the year 2021, followed by 24 in 2022. They were cited a total of 56661 times (average - 566.61 times). The 242 authors of these HCPs were from 159 Indian organizations, and the articles were published in 60 journals. 29 % and 59 % of these HCPs received external funding support and were involved in international collaborations, respectively. There was poor collaboration among Indian research institutions and a dearth of funding from India. None of the Indian HCPs figured in the global 100 HCPs., Conclusions: Although citations of research papers published from India increased during COVID-19, limited collaboration, inadequate funding, and subpar publications hindered Indian scientists. To enhance India's research landscape, we propose dismantling barriers, nurturing collaboration, and encouraging knowledge exchange among domestic institutions., Competing Interests: Declaration of competing interest All the authors hereby declare that there is conflict of interest regarding this manuscript & no funding was received from any source. We declare that this manuscript has been solely submitted to this journal and is not under consideration by any other journal. All the research presented in this paper is original., (Copyright © 2023 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Objectives : The objective of this consensus article was to form a list of expert recommendations and an easily adaptable algorithm for obesity management in India by primary care physicians (PCPs). Methods : A Delphi-based model was followed to form a list of the consensus recommendations. Consensus statements were created from the results of a literature review that were graded as per the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. After being evaluated by an expert panel comprising diabetologists, endocrinologists, cardiologists, bariatric surgeons, and gynecologists, the statements were revised and reevaluated by a larger group of practitioners, including PCPs and diabetologists, to arrive at a consensus. Results : The panel opined that obesity is increasing in prevalence in India and is projected to rise in the coming years. Body mass index and waist circumference were both recommended for better identification of people at risk of obesity-related comorbidities than either of them alone. The Edmonton Obesity Staging System (EOSS) was suggested as being most suitable for the assessment (staging) of obesity. A multidisciplinary team was considered invaluable for assessing and managing patients with obesity. The use of once-a-week semaglutide (2.4 mg) via the subcutaneous route was suggested as the first-choice anti-obesity treatment when pharmacotherapy is deemed necessary. An algorithm considering all these aspects was proposed. Conclusion : Obesity needs to be recognized as a significant contributor to other comorbidities. The diagnosis and management of obesity should be comprehensive and consider patient psychology, the presence or absence of comorbidities, available pharmacologic agents, and long-term outcomes. The proposed algorithm could help clinicians in this aspect and improve the overall outcomes. How to cite this article : Deshpande NR, Kapoor N, Dalal JJ, et al. Consensus on Current Landscape and Treatment Trends of Obesity in India for Primary Care Physicians. J Assoc Physicians India 2023;71(10):69-77., (© Journal of the Association of Physicians of India 2023.)

Background and Aims: There is a bidirectional relationship between COVID-19 and diabetes. The primary objective of this study was to estimate the prevalence of patients newly detected to have diabetes (NDD) who recovered from COVID-19 in India whilst comparing NDD with patients without diabetes (ND) and those who have known to have diabetes (KD) in terms of glycemic status pre- and post-COVID with disease severity., Materials & Methodology: There were 2212 participants enrolled from 15 sites, with 1630 active participants after the respective execution of selection criteria. Data collection was done using a specialized Case Record Form (CRF). Planned statistical analysis and descriptive statistics were concluded for significance between patient groups on various parameters., Result: The differences in age between the study groups were statistically significant. The average blood glucose at COVID-19 onset was significantly higher in KD than in NDD. Significantly more proportion of NDD (83%) had been hospitalized for COVID management when compared to KD (45%) and ND (55%). The NDD group received higher doses of steroids than the other two groups. On average, patients in the NDD group who received at least one vaccination (one dose or two doses) had a higher High-Resolution Computed Tomography (HRCT) score. Patients who had not been vaccinated in ND and KD groups experienced a higher HRCT score., Conclusion: Prospective metabolism studies in post-acute COVID-19 will be required to understand the etiology, prognosis, and treatment opportunities., (Copyright © 2022 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Objectives: To compare the efficacy of azithromycin versus doxycycline in treatment of children with uncomplicated scrub typhus in terms of percentage of children who attained remission of fever after 72 hours of administration of first dose of the study drug, mean time taken to attain fever defervescence, normalization of laboratory parameters, resolution of hepatosplenomegaly and lymphadenopathy., Design: Interventional, open-labeled randomized controlled trial., Study Methods: Patients admitted with undifferentiated fever in the In-Patient Department (IPD), Department of Paediatrics, All India Institute of Medical Sciences, Bhubaneswar, India, as per the inclusion criteria were randomized and was treated with azithromycin at 10 mg/kg/d in one group and doxycycline at 4.4 mg/kg/d for 5 days in the other group and was assessed based on the primary and secondary objectives., Results: There was no statistically significant difference between the percentage of children who attained remission of fever after 72 hours of administration of azithromycin (98.2%) and doxycycline (96.5%) (P value 0.47) and the average time taken for fever defervescence (azithromycin: 24.53 hours; doxycycline: 25.82 hours; P value 0.36). The odds of attaining fever remission in the doxycycline group as compared with the azithromycin group was 1.01 (95% confidence interval -0.60 to -1.71), which was also statistically not significant. There was less incidence of adverse drug events in the azithromycin group (1.78%) as compared with the doxycycline group (8.6%), which was statistically significant (P value 0.02)., Conclusion: Azithromycin is equally efficacious in terms of fever defervescence, resolution of clinical signs and laboratory parameters as doxycycline, is safer and better tolerated in children., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The genetic association studies of type 2 diabetes mellitus (T2DM) hitherto undertaken among the Indian populations are grossly inadequate representation of the ethnic and geographic heterogeneity of the country. In view of this and due to the inconsistent nature of the results of genetic association studies, it would be prudent to undertake large scale studies in different regions of India considering wide spectrum of variants from the relevant pathophysiological pathways. Given the reproductive dysfunctions associated with T2DM, it would be also interesting to explore if some of the reproductive pathway genes are associated with T2DM. The present study is an attempt to examine these aspects in the southern Indian population of Hyderabad., Methods: A prioritized panel of 92 SNPs from a large number of metabolic and reproductive pathway genes was genotyped on 500 cases and 500 controls, matched for ethnicity, age and BMI, using AGENA MassARRAYiPLEX™ platform., Results: The allelic association results suggested 14 SNPs to be significantly associated with T2DM at P ≤ 0.05 and seven of those-rs2241766-G (ADIPOQ), rs6494730-T (FEM1B), rs1799817-A and rs2059806-T (INSR), rs11745088-C (FST), rs9939609-A and rs9940128-A (FTO)-remained highly significant even after correction for multiple testing. A great majority of the significant SNPs were risk in nature. The ROC analysis of the risk scores of the significant SNPs yielded an area under curve of 0.787, suggesting substantial power of our study to confer these genetic variants as predictors of risk for T2DM., Conclusions: The associated SNPs of this study are known to be specifically related to insulin signaling, fatty acid metabolism and reproductive pathway genes and possibly suggesting the role of overlapping phenotypic features of insulin resistance, obesity and reproductive dysfunctions inherent in the development of diabetes. Large scale studies involving gender specific approach may be required in order to identify the precise nature of population and gender specific risk profiles for different populations, which might be somewhat distinct., (© 2021. The Author(s).)

Continuous and multi-year (2008-2012) measurements of black carbon (BC) mass concentrations (M BC ), carried out from the semiarid tropical site Udaipur (24.6° N, 74° E, 580 m a.s.l.) near the western Indian desert, are analyzed for their region-specific features. M BC varied over a wide range during the period of study, with the hourly mean values occurring as low as 0.09 to as high as 49.1 μg m -3 , with the multi-year average ~ 4.5 ± 2.6 μg m -3 . Annual variations showed the highest concentrations during November and December (winter seasonal mean = 7.4 ± 3.3 μg m -3 ) and the lowest in the monsoon months of July and August (monsoon seasonal mean = 2.5 ± 2.2 μg m -3 ). M BC showed significant inverse relationship with the planetary boundary layer height (ρ ~ - 0.50) as well as ventilation coefficient (ρ ~ - 0.72). Alike aforesaid atmospheric dynamic parameters, T, WS, and RH also possessed statistically significant negative correlations with monthly M BC . Enhancement in annual as well as diurnal amplitude in M BC during deficient monsoon years relative to excessive monsoon years have given marked indication of BC sink mechanism due to precipitation. Roles of long-range regional air pollutant transport also have been identified. Identical and consistent seasonal variation in percentage contribution of M BC with PM 2.5 (varying from 2.6 to 9.1%) and absorption Angstrom exponent (α abs , monthly mean values varying from 0.77 ± 0.04 to 1.16 ± 0.08) gives evidence of substantial amount of enhanced anthropogenic source activities of fossil fuel incomplete combustion in post-monsoon and winter period.

Background: Ivermectin is one among several potential drugs explored for its therapeutic and preventive role in SARS-CoV-2 infection. The study was aimed to explore the association between ivermectin prophylaxis and the development of SARS-CoV-2 infection among healthcare workers., Methods: A hospital-based matched case-control study was conducted among healthcare workers of AIIMS Bhubaneswar, India, from September to October 2020. Profession, gender, age and date of diagnosis were matched for 186 case-control pairs. Cases and controls were healthcare workers who tested positive and negative, respectively, for COVID-19 by RT-PCR. Exposure was defined as the intake of ivermectin and/or hydroxychloroquine and/or vitamin-C and/or other prophylaxis for COVID-19. Data collection and entry was done in Epicollect5, and analysis was performed using STATA version 13. Conditional logistic regression models were used to describe the associated factors for SARS-CoV-2 infection., Results: Ivermectin prophylaxis was taken by 76 controls and 41 cases. Two-dose ivermectin prophylaxis (AOR 0.27, 95% CI, 0.15-0.51) was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Those involved in physical activity (AOR 3.06 95% CI, 1.18-7.93) for more than an hour/day were more likely to contract SARS-CoV-2 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis and hydroxychloroquine prophylaxis were not associated with SARS-CoV-2 infection., Conclusion: Two-dose ivermectin prophylaxis at a dose of 300 μg/kg with a gap of 72 hours was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Chemoprophylaxis has relevance in the containment of pandemic., Competing Interests: The authors have declared that no competing interests exist.

Development of coronary artery disease (CAD) is primarily due to the process of atherosclerosis, however the prognosis of CAD depends on pleiotropic effects of the genes located at 9p21.3 region. Genome wide association studies revealed association of variants in this region with CAD pathology. However, specific marker in predicting CAD development or progression is not yet identified. In the present study, 35 SNPs at 9p21.3 region, located in the cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) genes, were genotyped among 350 CAD cases and 480 controls from the southern Indian population of Hyderabad using fluidigm nanofluidic SNP genotyping system and the data were analyzed using PLINK and R softwares. Of the 35 SNPs analysed, only one SNP, rs7865618, was found to be highly significantly associated with CAD, even after correction for multiple testing (p = 0.008). The AG and GG genotypes of this SNP conferred 3.08 and 1.93 folds increased risk for CAD respectively. In particular, this SNP was significantly associated with severe anatomic (triple vessel disease p = 0.023) and phenotypic (acute coronary syndrome p = 0.007) categories of CAD. Pair wise SNP interaction analysis between the SNPs of 9p21.3 and 11q23.3 regions revealed significantly increased risk of three SNPs of 11q23.3 region that were not associated individually, in conjunction with rs7865618 of 9p21.3.

We explored genetic susceptibility profile of the South Indian women with a large set of SNPs and tested if the lack of association of type 2 diabetes genes with PCOS, recently observed in a number of studies, holds true for this Indian population and suggest probable universality of this phenomenon. A prioritized set of 92 SNPs that belong to important reproductive and metabolic pathway genes were genotyped on 250 PCOS cases and 299 ethnically matched controls, representing the southern Indian population of Hyderabad, using SEQUENOM MassARRAY iPLEX™ platform. These data were analyzed both for individual SNP association patterns as well as for gene-gene interactions, besides obtaining cumulative risk score and the ROC curve with the help of appropriate statistical packages such as PLINK, SNPAssoc of R-program, Haploview, GMDR and SPSS. The analysis of 72 of the 92 SNPs, after excluding 20 of those that showed either minor allele frequency < 1% and/or deviated from Hardy Weinberg Equilibrium (p < .001), suggested that only 13 were associated with PCOS at p ≤ .05, but none after correction for multiple testing. Further, neither any of the diabetic genes nor the interactions between diabetic and reproductive pathway genes were found to be significant even at p ≤ .05.The lack of association of any of the SNPs with PCOS and/or the gene-gene interactions among them may be because of the minor effects of each of them on the phenotype(OR < 2). Further, that none of the type 2 diabetes genes were associated with PCOS in the present study as well as in the earlier studies from different ethnic groups may indicate probable universality of this pattern. It is possible that there are still other genetic variants, novel as well as already known, which may confer greater risk than the ones considered in this study and further studies are warranted to ascertain this both in the present population as well as in other ethnic and/or geographic groups of the Indian subcontinent., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this review, we briefly outlined salient features of pathophysiology and results of the genetic association studies hitherto conducted on type 2 diabetes. Primarily focusing on the current status of genomic research, we briefly discussed the limited progress made during the post-genomic era and tried to identify the limitations of the post-genomic research strategies. We suggested reanalysis of the existing genomic data through advanced statistical and computational methods and recommended integrated genomics-metabolomics approaches for future studies to facilitate understanding of the gene-environment interactions in the manifestation of the disease. We also propose a framework for research that may be apt for determining the effects of urbanization and changing lifestyles in the manifestation of complex genetic disorders like type 2 diabetes in the Indian populations and offset the confounding effects of both genetic and environmental factors in the natural way.

Purpose: Numerous studies across multiple specialties have evaluated the impact of trial registration on quality of study reports and found significant improvements over several domains. However, the impact of mandatory trial registration on the quality of clinical trial protocols remains hitherto unexplored., Methods: We carried out a retrospective cohort study of clinical trial applications submitted to drug regulatory authority of India for initial review with the objective of comparing methodological characteristics of their protocols. Since trial registration was made mandatory in the country in June 2009, we selected two study periods as between January 2007 to May 2009 (Period I) and July 2009 to December 2011 (Period II). Seventy-five protocols were randomly selected using a computer-generated list for each study period, making a total of 150 protocols. Data on twelve key methodological characteristics were collected including clearly defined primary outcomes, randomization, blinding, use of control group, statistical methods, handling of withdrawals amongst others., Results: More than 3/4th of the trial applications in the two study periods were for new chemical entities and nearly 90% were pharmaceutical industry sponsored studies. Comparing the period before and after implementation of mandatory trial registration, description of clearly defined trial outcomes improved from nearly 42% to 80% (p<0.001), sample size justifications increased from 38% to 70% (p<0.001) and use of allocation concealment improved from 24% to 49% (p=0.001). Marked improvement was also noted for blinding, description of statistical methods and handling of withdrawals and dropouts. Remaining characteristics did not change significantly between the two study periods. The mean cumulative scores for the study protocols improved significantly from 7± 0.296 in the first period to 8.93± 0.346 (p<0.001) in the second period., Conclusions: Our study found a significant improvement in the methodological quality characteristics of the protocols particularly in elements related to minimization of bias and statistical methods, which could be attributed to mandatory trial registration. Overall, the significant improvement was limited to global clinical trials, and room for improvement was noted for two quality characteristics - proportion of randomized studies and trials adequately describing the generation of allocation sequence.

Pharmaceuticals, personal care products (PPCPs), and artificial sweeteners (ASWs) are contaminants of emerging concern commonly found in the aquatic environments. In India, studies reporting environmental occurrence of these contaminants are scarce. In this study, we investigated the occurrence and distribution of 15 PPCPs and five ASWs in the river and groundwater (used untreated as drinking water) at several sites along the Ganges River. Based on the measured groundwater concentrations, we estimated the life-long human health risk from exposure to PPCPs through drinking. In addition, we estimated the risk of exposure to PPCPs and ASWs in the river water for aquatic organisms. The sum of detected PPCPs in the river water ranged between 54.7-826 ng/L, with higher concentrations in the severely anthropogenically influenced middle and lower reaches of the Ganges. The highest concentration among the PPCPs in the river water was of caffeine (743 ng/L). The sum of detected ASWs in river water ranged between 0.2-102 ng/L. Similar to PPCPs, the sum of ASWs in the river water was higher in the middle and lower reaches of the Ganges. In groundwater, the sum of detected PPCPs ranged between 34-293 ng/L, whereas of ASWs ranged between 0.5-25 ng/L. Negligible risk for humans was estimated from PPCPs in the drinking groundwater sources along the Ganges River, whereas moderate risks to PPCPs and ASWs (namely: caffeine, sulfamethoxazole, triclocarban, triclosan, and sucralose) were estimated for aquatic organisms in the Ganges River., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background/aim: Optimal cutoff values are influenced by ethnicity, geography, lifestyles, and physical activity, and hence, there is a need for establishing population- and disease-specific cutoff values to screen individuals/populations. Therefore, the present study was carried out to determine the optimal cutoff values of anthropometric variables for coronary artery disease (CAD) for the population of southern Andhra Pradesh., Methods: One hundred sixty five patients with CAD and 87 controls were recruited, and 52 anthropometric variables were measured for them., Results: Higher means in 22 anthropometric variables covering circumferences, skinfold thickness (sft), and indices were observed in patients than those in controls. Receiver operator curve analysis revealed that 18 variables including circumference, sft, and fat measures with an area under curve ranging from 0.61 to 0.72 were found to have the ability of predicting the risk of CAD. A stepwise discriminant analysis showed 9 variables to correctly classify 87.4% of subjects into CAD and controls. In logistic regression analysis, among these 9 variables, only circumferences of abdomen and foot; sft of supratellar, thigh and calf; and sum of subscapular/suprailiac, waist-hip ratio and lean body mass were associated with CAD and explained 73.4% of its variation., Conclusions: Eighteen anthropometric variables were found to have the ability of predicting the risk of CAD. Longitudinal studies are needed to confirm the use of anthropometric variables in predicting the risk of CAD., (Copyright © 2018 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background & Objectives: The genome-wide association studies (GWAS) have shown an association of type 2 diabetes mellitus (T2DM) with several novel genes. We report here the findings on the pattern of genetic association of three genes (CDKAL1, CDKN2A/B and HHEX) with T2DM in the population of Hyderabad, south India., Methods: A sample of 1379 individuals (758 T2DM cases and 621 controls) from Hyderabad, India, were genotyped for five single nucleotide polymorphisms (SNPs) of CDKAL1 (rs7754840, rs7756992) CDKN2A/B (rs10811661) and HHEX (rs1111875, rs7923837) genes on Sequenom Mass Array platform., Results: The risk allele frequencies of the CDKAL1 and CDKN2A/B SNPs were relatively higher in cases than in the controls and the logistic regression analysis yielded significant odds ratios suggesting that the variant alleles conferred risk for developing T2DM in this population. the HHEX gene did not show either allelic or genotypic association with T2DM. The multivariate logistic regression analysis with reference to both alleles and genotypes of CDKAL1 SNPs showed significant association, suggesting an important role for this gene in the T2DM pathophysiology., Interpretation & Conclusions: A significant association was seen of all the three SNPs of CDKAL1 and CDKN2A/B genes with T2DM but none of the two SNPs of HHEX. Further studies are required to cross-validate our findings in a relatively larger sample. It is also necessary to explore other SNPs of HHEX gene to unequivocally establish the pattern of association of this gene with T2DM in this population.

Background: We attempted to validate earlier findings on the nature of the association of the IRS1, CAPN10, and PPARG genes with type 2 diabetes mellitus (T2DM) in the high-risk population of Hyderabad, India., Methods: A sample of 1379 subjects (758 T2DM patients, 621 controls) was genotyped for single nucleotide polymorphisms (SNPs) of the IRS1 (rs1801278), CAPN10 (rs3792267, rs5030952), and PPARG (rs1801282) genes., Results: The allele and genotype frequencies of IRS1 (rs1801278) and CAPN10 (rs3792267) SNPs differed significantly between the patient and control groups. Logistic regression analysis suggested a significant association of these two SNPs (P ≤ 0.007) with T2DM and the strength of association did not alter when adjusted for age, gender, body mass index, and the waist : hip ratio as covariates. The same two SNPs showed significant association in multivariate logistic regression analyses, even after Bonferroni correction for multiple testing, suggesting an independent nature of the role of these genes in the manifestation of T2DM in our population., Conclusions: We replicated the significant association of rs1801278 and rs3792267 SNPs of the IRS1 and CAPN10 genes with T2DM in the population of Hyderabad. Despite the known biological significance of the PPARG gene and a sufficient statistical power of the present study, we could not replicate the association of PPARG with T2DM in our high-risk population. Given the vast ethnic, geographic, and genetic heterogeneity of the Indian population, many more studies are needed covering the ethnic and geographic heterogeneity of India to enable identification of an Indian-specific profile of genes associated with T2DM., (© 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

India's rapid agro-economic growth has resulted into many environmental issues, especially related to chemical pollution. Environmental management and control of toxic chemicals have gained significant attention from policy makers, researchers, and enterprises in India. The present study reviews the policy and legal and non-regulatory schemes set in place in this country during the last decades to manage chemical risk and compares them with those in developed nations. India has a large and fragmented body of regulation to control and manage chemical pollution which appears to be ineffective in protecting environment and human health. The example of POPs contamination in India is proposed to support such a theory. Overlapping of jurisdictions and retrospectively approached environmental policy and risk management currently adopted in India are out of date and excluding Indian economy from the process of building and participating into new, environmentally-sustainable market spaces for chemical products. To address these issues, the introduction of a new integrated and scientifically-informed regulation and management scheme is recommended. Such scheme should acknowledge the principle of risk management rather than the current one based on risk acceptance. To this end, India should take advantage of the experience of recently introduced chemical management regulation in some developed nations., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Polycystic Ovary Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a heterogeneous androgen excess disorder determined by the interaction of multiple genetic and environmental factors. Our earlier analysis on a panel of six candidate genes (Androgen receptor CAG repeats, Follistatin, Luteinizing hormone β subunit, Calpain10, Insulin receptor substrate-1 and PPARγ) based on 250 PCOS cases and 299 controls revealed significant association patterns with PCOS among South-Indian women. We report here for the first time, the SNP-SNP and SNP-environment interactions of these genes in the same cohort. Both multivariate logistic regression as well as epistasis analysis (using Multifactor dimensionality reduction software) yielded significant results (P < 0.05). All CAPN10 SNPs show association (either risk-conferring or protective) in the obese group, highlighting the importance of this gene in the PCOS pathophysiology. LHP7(LHβ) and UCSNP44(CAPN10) emerged to be the prominent SNPs in the SNP-SNP interaction analysis. The best SNP-SNP interaction model was obtained between CAPN10 UCSNP-44 and PPARγ His447His, implying a significant metabolic component in the PCOS pathology. Replicating our findings in BMI-specific cohorts in different ethnic populations would be warranted in future to identify the physiological networks in PCOS., (© 2013 John Wiley & Sons Ltd/University College London.)

We attempt to evaluate the nature of association of TCF7L2 gene variants with T2DM, for the first time in the population of Hyderabad, which is considered to be diabetic capital of India. It is a case-control study of the three SNPs of TCF7L2, rs7903146, rs12255372 and rs11196205, genotyped on Sequenom Massarray platform, in a sample of 758 patients and 621 controls. The risk allele frequency of the three SNPs was found to be significantly higher in the T2DM cases than controls, implicating susceptibility for diabetes (p<0.01). The greatest risk of developing the disease was conferred by rs7903146. Further, the logistic regression of genotypes of each SNP under log additive model, and the haplotypes constituted by at least one of the three risk alleles also show significantly greater risk of developing T2DM when compared to the wild type haplotype. Further, BMI and WHR emerge as significant covariates with confounding effects. The strong association of the TCF7L2 SNPs with T2DM is consistent with the findings among other Indian and Non-Indian populations, suggesting universal phenomena of its association across ethnic groups globally, both within and outside the Indian subcontinent, albeit the functional relevance of these SNPs needs yet to be established.

Polycystic ovary syndrome is known to be characterized by metabolic abnormalities such as hyperinsulinemia, adiposity and dyslipidemia. Both insulin receptor substrate-1 and peroxisome proliferator-activated receptor-γ have emerged as significant candidate genes in the pathogenesis of PCOS. In this study, we report for the first time, the association pattern of these genes with PCOS among South Indian women. Two hundred fifty PCOS cases and 299 controls were sequenced for IRS-1 exon1 and PPAR-γ exon 2 and exon 6 to study the already reported SNPs in other ethnic groups and to identify any novel SNP in these exonic regions specific to the Indian population. We did not find any novel SNP in our population except for those already reported- two IRS-1 polymorphisms (Gly972Arg and G2323A) and two PPAR-γ polymorphisms (Pro12Ala and His447His). While the IRS-1 polymorphic alleles had a similar distribution between cases and controls, the PPAR-γ exon 2 Ala allele and exon 6 His447His T allele were significantly more in the controls than in the cases (p≤0.05). Haplotype association analysis also suggests that both IRS-1 and PPAR-γ haplotypes with mutations depicted reduced frequency of hyperandrogenic and metabolic traits in PCOS compared to the haplotype with only wild type alleles. Our study on Indian women suggests that while IRS-1, contrary to the earlier findings in other ethnic groups, seems to have a probable protective role against development of specific PCOS sub-phenotypes, the evidence for a probable protective role of PPAR-γ is reaffirmed in our study., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Abnormal luteinizing hormone (LH) secretion and action are known to affect ovarian steroidogenesis and thus playing a crucial role in manifestation of polycystic ovary syndrome (PCOS). This study is first of its kind to study association of LH β-subunit gene variants with PCOS among South-Indian women. 250 PCOS cases and 299 controls were recruited for the study. All the exons of LH β gene were screened. Allele and genotype frequencies of the SNPs were compared between the cases and controls. We identified seven SNPs in the LH β gene; one SNP in exon 3 (rs#1056917) exhibited significant difference in the allele frequency between the PCOS cases and controls (p=0.015). Although, the LH β variants that are found to be more frequent among PCOS cases are silent in nature and not of any functional significance, they might influence other significant functional polymorphisms in the hypothalamic-pituitary-gonadal axis which needs to be explored., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Polycystic Ovary Syndrome (PCOS) is known to be characterized by metabolic disorder in which hyperinsulinemia and peripheral insulin resistance are central features. Given the physiological overlap between PCOS and type-2 diabetes (T2DM), and calpain 10 gene (CAPN10) being a strong candidate for T2DM, a number of studies have analyzed CAPN10 SNPs among PCOS women yielding contradictory results. Our study is first of its kind to investigate the association pattern of CAPN10 polymorphisms (UCSNP-44, 43, 56, 19 and 63) with PCOS among Indian women. 250 PCOS cases and 299 controls from Southern India were recruited for this study. Allele and genotype frequencies of the SNPs were determined and compared between the cases and controls. Results show significant association of UCSNP-44 genotype CC with PCOS (p = 0.007) with highly significant odds ratio when compared to TC (OR = 2.51, p = 0.003, 95% CI = 1.37-4.61) as well as TT (OR = 1.94, p = 0.016, 95% CI = 1.13-3.34). While the haplotype carrying the SNP-44 and SNP-19 variants (21121) exhibited a 2 fold increase in the risk for PCOS (OR = 2.37, p = 0.03), the haplotype containing SNP-56 and SNP-19 variants (11221) seems to have a protective role against PCOS (OR = 0.20, p = 0.004). Our results support the earlier evidence for a possible role of UCSNP-44 of the CAPN10 gene in the manifestation of PCOS.

Several genetic factors have been found to be associated with recurrent pregnancy loss (RPL). However, not many attempts have been made to associate the mitochondrial DNA (mtDNA) variations with RPL. Therefore, we have analyzed the complete mtDNA of 100 women with RPL and 12 aborted fetal tissues. Our analysis revealed a total of 681 variations, most of which were in NADH Dehydrogenase (ND) genes that encode mitochondrial enzyme Complex I. Presence of T4216C variation (ND1 gene) in 9% of the RPL women and several pathogenic, and novel mutations suggest the role of mtDNA variations in RPL., (Copyright © 2011 © Elsevier B.V. and Mitochondria Research Society. All rights reserved. Published by Elsevier B.V. All rights reserved.)

BACKGROUND In this study, recurrent miscarriages (RMs) are defined as loss of two or more clinically detectable pregnancies before 20 weeks of gestation. HLA has been thought to play a role in RM. However, the results of earlier studies on the role of different human leucocyte antigen (HLA) genes were conflicting and inconclusive. In the present study, we investigate HLA genes (HLA-DRA, HLA-DRB1, HLA-DQA1 and HLA-DQB1) in RM couples with unknown etiology and normal couples. METHODS Blood samples from 143 RM couples and 150 control couples were analyzed, firstly to validate previously reported association studies and secondly to explore whether any novel alleles or haplotypes specific to Indian populations can be observed to be associated with RM. HLA typing was carried out by DNA sequencing. RESULTS Results suggest an association of the DQB1*03:03:02 allele with RM (odd ratio = 2.66; p(c) = 0.02; confidence interval = 1.47-4.84). Haplotypes of the DQA1 and DQB1 risk alleles also showed a significant association with RM, albeit not after Bonferroni correction for multiple comparisons. CONCLUSIONS HLA-DQB1 appears to have a strong involvement in the manifestation of RM in this population from South India. The current genetic analysis of RM and control couples not only highlights the genes exhibiting a strong etiological role but also reflects the protective nature of some HLA genes against RM. Nevertheless, most of these alleles/haplotypes were not those that are implicated in RM in other ethnic backgrounds, and hence require further validation in other populations of India, from different ethnic and/or geographic backgrounds.

The aim of the present study was to investigate the role of CAG repeat polymorphism and X-chromosome Inactivation (XCI) pattern in Recurrent Spontaneous Abortions among Indian women which has not been hitherto explored. 117 RSA cases and 224 Controls were included in the study. Cases were recruited from two different hospitals--Lakshmi Fertility Clinic, Nellore and Fernandez Maternity Hospital, Hyderabad. Controls were roughly matched for age, ethnicity and socioeconomic status. The CAG repeats of the Androgen Receptor gene were genotyped using a PCR-based assay and were analysed using the GeneMapper software to determine the CAG repeat length. XCI analysis was also carried out to assess the inactivation percentages. RSA cases had a significantly greater frequency of allele sizes in the polymorphic range above 19 repeats (p = 0.006), which is the median value of the controls, and in the biallelic mean range above 21 repeats (p = 0.002). We found no evidence of abnormal incidence of skewed X-inactivation. We conclude that longer CAG repeat lengths are associated with increased odds for RSA with statistical power estimated to be ∼90%.

Background: It has been observed that menstrual characteristics are generally influenced by lifestyle, socio-cultural and biological factors., Aim: The present study examines: (a) variation in menstrual characteristics between rural and urban adolescents; and (b) whether these characteristics can be predicted from various socio-economic variables related to place of residence., Subjects and Methods: The sample of the present study constituted 715 adolescent girls from rural (325) and urban (390) areas of West Bengal, a State of India. These girls belong to a Bengali-speaking Hindu ethnic group. Data on socio-economic variables and menstrual characteristics were collected using pretested questionnaires., Results: Rural and urban adolescents differed significantly (p < or = 0.05) with respect to age at menarche, skipped and irregular cycles, premenstrual syndrome, duration of menstrual discharge, mean number of days of peak discharge and problems related to menstrual discharge. Place of residence was found to be a significant predictor of age at menarche (beta = 0.27, p < 0.01). Significant association was observed between some of the socio-economic variables and various menstrual characteristics among the study participants., Conclusions: Menstrual characteristics differ significantly between rural and urban adolescents. Moreover, various socio-economic variables pertaining to place of residence significantly affect the menstrual characteristics among adolescents.

The present study was carried out to assess the role of androgen receptor CAG repeat polymorphism and X chromosome inactivation (XCI) pattern among Indian PCOS women and controls which has not been hitherto explored and also to test the hypothesis that shorter CAG alleles would be preferentially activated in PCOS. CAG repeat polymorphism and X chromosome methylation patterns were compared between PCOS and non-PCOS women. 250 PCOS women and 299 controls were included for this study. Androgen receptor CAG repeat sizes, XCI percentages, and clinical and biochemical parameters were measured. The mean CAG repeat number is similar between the cases (18.74±0.13) and controls (18.73±0.12). The obese PCOS women were significantly more frequent in the <18 and >20 CAG repeat category than the lean PCOS women, yielding a highly significant odds (p=0.001). Among the women with non-random X-inactivation, alleles with <19 repeats were more frequently activated among cases than controls (p=0.33). CAG repeat polymorphism by itself cannot be considered as a useful marker for discriminating PCOS. We observed a trend of preferential activation of the shorter allele among the PCOS cases with non random XCI pattern. In the obese PCOS women, this microsatellite variation may account for the hyperandrogenicity to a larger extent than the lean PCOS women.

For historical reasons, the Indian subcontinent is endowed with enormous ethnic, cultural, and genetic heterogeneity of its people. In the process of understanding the dynamics and sociocultural complexity of Indian society, anthropologists have come up with a number of hypotheses involving certain social/cultural processes that may modulate evolutionary processes. In this article, we outline some of those hypotheses and present molecular genetic evidences, both published and unpublished, to demonstrate the effects of those social/cultural processes.

Background: We attempt to ascertain if the 3 linked single nucleotide polymorphisms (SNPs) of the Progesterone Receptor (PR) gene (exon 1: G 1031 C; S344T, exon 4: G 1978 T; L660V and exon 5: C 2310 T; H770H) and the PROGINS insertion in the intron G, between exons 7 and 8, are associated with Recurrent Spontaneous Abortion (RSA) in the Indian population., Methodology/principal Findings: A total of 143 women with RSA and 150 controls were sequenced for all the 8 exons looking for the above 3 linked SNPs of the PR gene earlier implicated in the RSA, as well as for any new SNPs that may be possibly found in the Indian population. PROGINS insertion was screened by electrophoresis. We did not find any new mutations, not observed earlier, in our population. Further, we did not find significant role of the *2 allele (representing the mutant allele at the three SNP loci) or the T2 allele (PROGINS insertion) in the manifestation of RSA. We also did not find an LD pattern between each of the 3 SNPs and the PROGINS insertion., Conclusions/significance: The results suggest that the PR gene mutations may not play any exclusive role in the manifestation of RSA, and instead, given significantly higher frequency of the *2 allele among the normal women, we surmise if it does not really confer a protective role among the Indian populations, albeit further studies are required in the heterogeneous populations of this region before making any conclusive statement.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age with a prevalence of approximately 7-10% worldwide. PCOS reflects multiple potential aetiologies and variable clinical manifestations. This syndrome is characterized by serious health implications such as diabetes, coronary heart diseases and cancer and also leads to infertility. PCOS can be viewed as a heterogeneous androgen excess disorder with varying degrees of reproductive and metabolic abnormalities determined by the interaction of multiple genetic and environmental factors. In this paper, we have attempted a comprehensive review of primarily molecular genetic studies done so far on PCOS. We have also covered the studies focusing on the environmental factors and impact of ethnicity on the presentation of this syndrome. A large number of studies have been attempted to understand the aetiological mechanisms behind PCOS both at the clinical and molecular genetic levels. In the Indian context, majority of the PCOS studies have been confined to the clinical dimensions. However, a concrete genetic mechanism behind the manifestation of PCOS is yet to be ascertained. Understanding of this complex disorder requires comprehensive studies incorporating relatively larger homogenous samples for genetic analysis and taking into account the ethnicity and the environmental conditions of the population/cohort under study. Research focused on these aspects may provide better understanding on the genetic etiology and the interaction between genes and environment, which may help develop new treatment methods and possible prevention of the syndrome.

Exertional heat illness is primarily a multi-system disorder results from the combined effect of exertional and thermoregulation stress. The severity of exertional heat illness can be classified as mild, intermediate and severe from non-specific symptoms like thirst, myalgia, poor concentration, hysteria, vomiting, weakness, cramps, impaired judgement, headache, diarrhea, fatigue, hyperventilation, anxiety, and nausea to more severe symptoms like exertional dehydration, heat cramps, heat exhaustion, heat injury, heatstroke, rhabdomyolysis, and acute renal failure. At its early stage, it is quite difficult to find out the severity of disease with manual screening because of overlapping of symptoms. Therefore, one need to classify automatically the disease based on symptoms. The 7:10:1 backpropagation artificial neural network model has been used to predict the clinical outcome from the symptoms that are routinely available to clinicians. The model has found to be effective in differentiating the different stages of exertional heat-illness with an overall performance of 100%.

Northeast India, the only region which currently forms a land bridge between the Indian subcontinent and Southeast Asia, has been proposed as an important corridor for the initial peopling of East Asia. Given that the Austro-Asiatic linguistic family is considered to be the oldest and spoken by certain tribes in India, Northeast India and entire Southeast Asia, we expect that populations of this family from Northeast India should provide the signatures of genetic link between Indian and Southeast Asian populations. In order to test this hypothesis, we analyzed mtDNA and Y-Chromosome SNP and STR data of the eight groups of the Austro-Asiatic Khasi from Northeast India and the neighboring Garo and compared with that of other relevant Asian populations. The results suggest that the Austro-Asiatic Khasi tribes of Northeast India represent a genetic continuity between the populations of South and Southeast Asia, thereby advocating that northeast India could have been a major corridor for the movement of populations from India to East/Southeast Asia.

Background: India is a country with enormous social and cultural diversity due to its positioning on the crossroads of many historic and pre-historic human migrations. The hierarchical caste system in the Hindu society dominates the social structure of the Indian populations. The origin of the caste system in India is a matter of debate with many linguists and anthropologists suggesting that it began with the arrival of Indo-European speakers from Central Asia about 3500 years ago. Previous genetic studies based on Indian populations failed to achieve a consensus in this regard. We analysed the Y-chromosome and mitochondrial DNA of three tribal populations of southern India, compared the results with available data from the Indian subcontinent and tried to reconstruct the evolutionary history of Indian caste and tribal populations., Results: No significant difference was observed in the mitochondrial DNA between Indian tribal and caste populations, except for the presence of a higher frequency of west Eurasian-specific haplogroups in the higher castes, mostly in the north western part of India. On the other hand, the study of the Indian Y lineages revealed distinct distribution patterns among caste and tribal populations. The paternal lineages of Indian lower castes showed significantly closer affinity to the tribal populations than to the upper castes. The frequencies of deep-rooted Y haplogroups such as M89, M52, and M95 were higher in the lower castes and tribes, compared to the upper castes., Conclusion: The present study suggests that the vast majority (> 98%) of the Indian maternal gene pool, consisting of Indio-European and Dravidian speakers, is genetically more or less uniform. Invasions after the late Pleistocene settlement might have been mostly male-mediated. However, Y-SNP data provides compelling genetic evidence for a tribal origin of the lower caste populations in the subcontinent. Lower caste groups might have originated with the hierarchical divisions that arose within the tribal groups with the spread of Neolithic agriculturalists, much earlier than the arrival of Aryan speakers. The Indo-Europeans established themselves as upper castes among this already developed caste-like class structure within the tribes.

The extent of population subdivision based on 15 Y-chromosome polymorphisms was studied in seven subcastes of the Golla (Karnam, Pokanati, Erra, Doddi, Punugu, Puja, and Kurava), who inhabit the Chittoor district of southern Andhra Pradesh, India. These Golla subcastes are traditionally pastoralists, culturally homogeneous and endogamous. DNA samples from 146 Golla males were scored for seven unique event polymorphisms (UEPs) and eight microsatellites, permitting allocation of each into haplogroups and haplotypes, respectively. Genetic diversity (D) was high (range, 0.9048-0.9921), and most of the genetic variance (>91%) was explained by intrapopulation differences. Median-joining network analysis of microsatellite haplotypes demonstrated an absence of any structure according to subcaste affiliation. Superimposition of UEPs on this phylogeny, however, did create some distinct clusters, indicating congruence between haplotype and haplogroup phylogenies. Our results suggest many male ancestors for the Golla as well as for each of the subcastes. Genetic distances among the seven subcastes, based on autosomal markers (short tandem repeats and human leukocyte antigens) as well as those on the chromosome Y, indicate that the Kurava may not be a true subcaste of the Golla. Although this finding is based on a very small Kurava sample, it is in accordance with ethnohistorical accounts related by community elders. The Punugu was the first to hive off the main Golla group, and the most recently separated subcastes (Karnam, Erra, Doddi, and Pokanati) fissioned from the Puja. This phylogeny receives support from the analysis of autosomal microsatellites as well as HLA loci in the same samples. In particular, there is a significant correlation (r = 0.8569; P = 0.0097) between Y-chromosome- and autosomal STR-based distances.

In the present study, we analyzed 1,686 samples from 31 tribal populations of India for the mitochondrial DNA 9-base-pair deletion/insertion polymorphism, and characterized them based on the relevant mitochondrial DNA coding-region single nucleotide polymorphisms and hypervariable region I motifs, to test the genetic origins of the ethnically and linguistically heterogeneous Austro-Asiatic tribes of India. A comparative analysis of our results with the existing data suggests multiple origins of Austro-Asiatic tribes in India, and particularly the Asian and non-Asian origins of the Mon-Khmer and the Mundari populations. We also identified a novel subclade of haplogroup B in the Mon-Khmer Khasi tribes that distinguishes them from the Nicobarese, indicating two different waves of migration of the Mon-Khmer tribes in India.

DNA samples of 948 individuals belonging to 27 populations from southern Andhra Pradesh were analyzed for nine AmpFlSTR Profiler Plus loci. The nature and extent of genomic diversity within and between these populations have been examined with reference to socioeconomic and geographic affiliations. The results suggest that the average heterozygosity is uniformly high in these populations (> 0.80) and that the patterns of allele distributions are similar across the populations. The value of the coefficient of gene differentiation and the AMOVA and structure analysis results suggest that these populations are highly homogeneous. The neighbor-joining tree constructed using either D(A) or F(ST) distances suggests no intelligible pattern of population clusters based on ethnohistoric or geographic affiliations. All these observations suggest either a common recent origin of these populations or extensive gene flow across the populations that erased the original genetic differences. Given strict endogamy, the latter explanation can hold only if there has been unauthorized or unrecognized gene flow transecting the social boundaries. Nevertheless, the regression plot of average heterozygosity versus distance from the centroid (Rii), based on Harpending and Ward's (1982) model, and the genetic distances computed between different hierarchical groups within Andhra Pradesh tend to support this conjecture. Overall, the results suggest lack of a significant degree of genetic stratification that is consistent with social stratification in Andhra Pradesh. Furthermore, the neighbor-joining tree based on comparative data from other Indian and continental populations brings out a single and compact cluster of all the Andhra populations that is clearly separated from the rest.

The autosomal AmpFLSTR markers validated and widely used for forensic applications are used in this study to examine the extent of diversity and genetic relationships among nine Meghalaya populations. Altogether, 932 chromosomes from 9 populations were analyzed using 9 tetrameric AmpFLSTR loci. The included populations were all seven subtribes of the Austro-Asiatic Mon-Khmer-speaking Khasi and the neighboring Tibeto-Burman Garo. The Lyngngam, which are linguistically closer to the Khasi but are culturally intermediate between the Khasi and the Garo, are also included in the study. Although most of the microsatellite loci are highly polymorphic in each of these populations, the allele distributions are fairly uniform across the Meghalaya populations, suggesting relative homogeneity among them. Concurrent with this, the coefficient of gene differentiation (G(ST)) is observed to be low (0.026+/-0.002). This is naturally reflected in the lack of clear differentiation and clustering pattern of the Meghalaya tribes based on either geographic proximity or the historical or current affiliations of these tribes. Analysis of molecular variance (AMOVA) suggests no significant population structure. The structure analysis further suggests that, barring War-Khasi and Pnar, no other population shows any semblance of genetic identity. Even the position of the linguistically distinct Garo is not portrayed as separate from the Khasi. However, when comparable data from other Indian, Southeast Asian, and other continental populations were analyzed, the Meghalaya populations formed a compact cluster clearly separated from other populations, suggesting genetic identity of the Meghalaya populations as a whole. These results are concurrent with the hypothesis of a common and recent origin of these Meghalaya populations, whose genetic differentiation is overwhelmed by the homogenizing effect of continuous gene flow.

We critically examined the gene frequency data for 11 genetic markers commonly available in the literature for 22 populations of northeastern India in the light of their geographic, linguistic, and ethnic affiliations. The markers investigated were three blood groups (A1A2BO, MNS, and Rh), four serum proteins (KM, Gc, Hp, and Tf), and four enzyme systems (AP, AK, EsD, and Hb). The neighbor-joining tree and multidimensional scaling of the distance matrix suggest relatively high genetic differentiation among the Mongoloid groups, with probably diverse origins when compared to the Caucasoid Indo-European populations, which had probably come from relatively more homogeneous backgrounds. Broadly speaking, the pattern of population affinities conforms to the ethno-historic, linguistic, and geographic backgrounds. An interesting and important feature that emerges from this analysis is the reflection of the effect of the sociological process of a Tribe-Caste continuum on genetic structure. While on one end we have the cluster of Caucasoid caste populations, the other end consists of Mongoloid tribal groups. In between are the populations which were originally tribes but now have become semi-Hinduized caste groups, viz., Rajbanshi, Chutiya, and Ahom. These groups have currently assumed caste status and speak Indo-European languages. Therefore, one may infer that what appears to be a purely sociological phenomenon of a Tribe-Caste continuum may well reflect in their genetic structure., (Copyright 2004 Wiley-Liss, Inc.)

Published data on palmar interdigital ridge counts (a-b, b-c, and c-d) among 57 populations from the Indian subcontinent were analyzed with reference to ethnic, socioeconomic, linguistic, and geographic affiliations of the studied populations. The spatial autocorrelation analysis suggests significant correlation between dermatoglyphic and geographic distances. The congruence with the ethnic semblance of the groups is also apparent in the data, and, in fact, the multiresponse permutation procedure did suggest highly significant within-group homogeneity, confirming the biological validity of the social and ethnic criteria used in the analysis. The plots of populations on the first two principal components, accounting for 92% of the total variance, complement and support the results based on the other analyses, which show certain ethnic and geographic patterns. These findings can serve as baseline information for future studies on population variation in India, particularly studies based on molecular genetic markers, a trend that has already gained momentum.

Among the most contentious currently debated issues is about the people who had settled first in the Indian subcontinent. It has been suggested that the communities affiliated to the Austro-Asiatic linguistic family are perhaps the first to settle in India and the palaeoanthropological evidences suggest the earliest settlement probably around 60,000 years BP. Recent speculations, based on both traditional genetic markers and DNA markers, seem to corroborate the aforesaid view. However, these studies are inadequate both in terms of the representation of the constituent groups within this broad linguistic category as well as the number of samples that represent each of them. We strongly feel that, before making any formidable conclusions on the peopling of India and/or the history of settlement, it is necessary to ascertain that the Austro-Asiatic speakers, represented by over 30 different tribal groups, either genetically constitute a homogenous single entity or are a heterogeneous conglomeration, derived from different sources. As a first step towards this we tried to collate and analyse the existing information geographic, ethno-historic, cultural and biological. The results of the analyses of anthropometric and genetic marker data indicate that the Austro-Asiatic groups, particularly the Mundari speakers, with certain exceptions, show greater homogeneity among them when compared to the other linguistic groups, although certain groups show as outliers. However, traditional genetic markers show lower within population heterozygosity compared to Dravidian and other Indian populations. This is contrary to what has been claimed in case of certain DNA markers. Given that relatively greater heterozygosity among the Austro-Asiatic populations has been taken as one of the important evidences supporting greater antiquity of these populations one should await results of detailed DNA studies being currently undertaken by us, involving a number of Austro-Asiatic and other ethnic populations of India to resolve the issue unequivocally.

Genetic diversity at the nine short tandem repeat (STR) loci, which are universally approved and widely used for forensic investigations, has been studied among nine Indian populations with diverse ethnic, linguistic, and geographic backgrounds. The nine STR loci were profiled on 902 individuals using fluorescent detection methods on an ABI377 System, with the aid of an Amp-F1 Profiler Plus Kit. The studied populations include two upper castes, Brahmin and Kayastha; a tribe, Garo, from West Bengal; a Hindu caste, Meitei, with historical links to Bengal Brahmins; a migrant group of Muslims; three tribal groups, Naga, Kuki and Hmar, from Manipur in northeast India; and a middle-ranking caste, Golla, who are seminomadic herders from Andhra Pradesh. Gene diversity analysis suggests that the average heterozygosity is uniformly high (>0.8) in the studied populations, with the coefficient of gene differentiation at 0.050 +/- 0.0054. Both neighbor-joining (NJ) and unweighted pair group method with arithmetic mean (UPGMA) trees based on DA distances bring out distinct clusters that are consistent with ethnic, linguistic, and/or geographic backgrounds of the populations. The fit of the Harpending and Ward model of regression of average heterozygosity on the gene frequency centroid is found to be good, and the observed outliers are consistent with the population structure and history of the studied populations. Our study suggests that the nine STR loci, used so far mostly for forensic investigations, can be used fruitfully for microevolutionary studies as well, and for reconstructing the phylogenetic history of human populations, at least at the local level.

Foot-and-mouth disease virus (FMDV) type O outbreaks have been reported frequently in vaccinated cattle in India. Twenty-five field isolates, recovered from outbreaks in vaccinated and unvaccinated cattle between 1987 and 1991, were analyzed in relation to the vaccine strain (R2/75) by complement fixation, serum neutralization and partial nucleotide sequencing of the VP1 gene. These sequences were compared with the viral sequences in GenEMBL database. Although the Indian type O viruses were close to the European type O1 viruses, they constituted a separate group of type O FMDVs. One of the field viruses, isolated from an outbreak in vaccinated cattle and designated as BAK/90, showed significant serological and nucleotide sequence variations from the vaccine strain. Phylogenetic analysis showed that the BAK/90 and R2/75 viruses belong to separate subgroups. The other isolates were found to be serologically related to both the BAK/90 and the vaccine strain. The BAK/90 strain gave broader antigenic coverage, showed better immunogenicity, and yielded larger amounts of 146S particles in suspension cultures as compared with R2/75. Taken together, these results favour inclusion of the BAK/90 strain in the vaccine to provide adequate protection against the field variants of type O FMDV currently circulating in India.