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CAD (Coronary Artery Disease) morbidity is becoming an endemic worldwide. Recently, the role of pro- and anti-inflammatory cytokines in the development of atherosclerotic plaques has been explored, but the association of their genetic polymorphisms and CAD has yet not been established. The present study aimed to investigate the association of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) polymorphisms and the risk of CAD in North Indian population. 1000 subjects (500 angiographically confirmed CAD patients and 500 controls) were genotyped by ARMS-PCR. Results revealed a significant risk association of both the polymorphisms with CAD. The heterozygous and the mutant genotypes of IL-8 rs4073 were both found to be associated with the risk of disease after adjusting for the confounders (padj < 0.001, ORadj 3.121, 95% CI 1.926-5.056 and padj < 0.001, ORadj 3.116, 95% CI 1.952-4.973, respectively), but only the mutant AA genotype of IL-10 rs1800872 correlated with risk of disease with padj < 0.001, ORadj 4.106, 95% CI 2.160-7.806). Stratifying the samples on the basis of gender revealed CAD in heterozygous and mutant in males (padj < 0.001, ORadj 3.693, 95% CI 2.031-6.716; padj < 0.001, ORadj 3.288, 95% CI 1.848-5.851, respectively) and only the mutant to be associated with risk of disease in females (padj = 0.010, ORadj 2.867, 95% CI 1.284-6.404) for IL-8 rs4073, whereas only the mutant genotype AA of IL-10 rs1800872 associated with CAD risk in males (padj < 0.001, ORadj 5.821, 95% CI 2.831-11.970). Stratified analysis based on age showed a significant higher risk in the heterozygous and mutant genotype in subjects below 40 years of age (padj = 0.039, ORadj 5.052, 95% CI 1.081-23.602; and padj = 0.025, ORadj 5.533, 95% CI 1.239-24.704, respectively) compared with the heterozygous and mutant genotype association of the risk of disease in subjects above 40 years of age (padj < 0.000, ORadj 2.964, 95% CI 1.747-5.027; and padj < 0.000, ORadj 2.859, 95% CI 1.716-4.762, respectively) in IL-8 rs4073. For IL-10 rs1800872, risk association was seen only in subjects above 40 years of age (padj < 0.001, ORadj 5.049, and 95% CI 2.414-10.561). The present study exhibited associations of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) with CAD in the North Indian population and also that the associations are gender and age dependent. [ABSTRACT FROM AUTHOR]

There is a drastic increase in the number of people suffering from coronary artery disease (CAD) worldwide with Indians being no exception. Being a developing country and experiencing a dramatic shift in lifestyle and eating habits, urbanization and industrialization, all these factors have collectively predisposed the Indian population towards CAD and the prevalence data are quite alarming. Genetic studies have disclosed the role of genes in CAD susceptibility and severity. One such gene is proprotein convertase subtilisin/kexin type 9 (PCSK9) which is sought to modulate the cholesterol levels and hence, has implications in CAD. We aim to explore the association of PCSK9 A/G (rs505151) polymorphism and hence, the susceptibility towards CAD in the north Indian population. Five-hundred angiographically confirmed CAD patients and 500 healthy individuals as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis revealed a significant association with the G allele with odds ratio (OR)=1.50, 95% confidence interval (CI)=1.22-1.85 and P=0.000. Also, a strong association was observed for CAD risk with OR=1.590, 95% CI=1.106-2.284 and P=0.012. However, the homozygous GG mutant genotype was found to be completely absent from our population. Analysis of the dominant model also revealed an association with CAD risk. Our work demonstrated for the first time the association of PCSK9 A/G (rs505151) polymorphism with CAD risk in the north Indian population. [ABSTRACT FROM AUTHOR]

Global gene expression profiling is a powerful tool enabling the understanding of pathophysiology and subsequent management of diseases. This study aims to explore functionally annotated differentially expressed genes (DEGs); their biological processes for coronary artery disease (CAD) and its different severities of atherosclerotic lesions. This study also aims to identify the change in expression patterns of DEGs in atherosclerotic lesions of single-vessel disease (SVD) and triple-vessel disease (TVD). The weight of different severities of lesion was estimated using a modified Gensini score. The gene expression profiling was performed using the Affymetrix microarray platform. The functional annotation for CAD was performed using DAVID v6.8. The biological network gene ontology tool (BiNGO) and ClueGO were used to explore the biological processes of functionally annotated genes of CAD. The changes in gene expression from SVD to TVD were determined by evaluating the fold change. Functionally annotated genes were found in an unique set and could be distinguishing two distinct severities of CAD. The biological processes such as cellular migration, locomotion, cell adhesion, cytokine production, positive regulation of cell death etc. enriched the functionally annotated genes in SVD, whereas, wound healing, negative regulation of cell death, blood coagulation, angiogenesis and fibrinolysis were enriched significantly in TVD patients. The genes THBS1 and CAPN10 were functionally annotated for CAD in both SVD and TVD. The 61 DEGs were identified, those have changes their expression with different severities of atherosclerotic lesions, in which 13 genes had more than two-fold change in expression between SVD and TVD. The consistent findings were obtained on validation of microarray gene expression of selected 10 genes in a separate cohort using real-time PCR. This study identified putative candidate genes and their biological processes predisposing toward and affecting the severity of CAD. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a metabolic pro-inflammatory disorder characterized by chronic hyperglycemia and increased levels of circulating cytokines suggesting a causal role of inflammation in its etiology. Polymorphism of cytokine genes including interleukin-6 ( IL- 6), tumour necrosis factor- α ( TNF- α) and interleukin-10 ( IL- 10) were studied in T2DM patients as well as in normal healthy controls. Genomic DNA was isolated from both T2DM patients and controls followed by quantification and genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using suitable primers. The genotypic, allelic and carriage rate frequency distribution in patients and controls were analyzed by SPSS (version 15.0). Odd ratios with 95 % confidence interval was determined to describe the strength of association by logistic regression model. Double and triple combinations of genotypes were analyzed by χ test. Gene-gene interaction and linkage disequilibrium tests were performed using SHEsis software. Individually, IL- 6, TNF- α and IL- 10 did not show any association. In double combination, IL- 6 −597 GA and TNF- α −308 GG genotypes increased the risk up to 21 times and in triple combination IL- 6 −597 AA, TNF- α −308 GG and IL- 10 −592 CA increased the risk of T2DM up to 314 times. In gene-gene interaction allele 'A' of all studied polymorphisms increased the risk of T2DM up to 1.41 times. Our results suggest that individuals having a haplotype combination of AA, GG and CA for IL- 6, TNF- α and IL- 10 gene polymorphisms will have higher susceptibility and be at greater risk of developing T2DM. [ABSTRACT FROM AUTHOR]

Background: A deletion of 287-bp Alu repeat of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene is associated with hypertension. Purpose: The aim of this study is to determine the frequency of ACE (I/D) polymorphism in patients with obstructive sleep apnea (OSA). Methods: Genotyping of ACE (I/D) gene polymorphism and estimation of serum angiotensin-converting enzyme (SACE) activity were done in 813 subjects who underwent polysomnography. Of these, 395 were apneics and 418 were non-apneics. Results: The frequencies of II genotype (OR = 1.8, 95 % CI 1.26-2.60, p = 0.001) and I allele (OR = 1.4, 95 % CI 1.13-1.69, p = 0.001) of ACE gene were found to be significantly increased in patients with OSA as compared to patients without OSA. Frequency of II genotype was significantly decreased (OR = 0.46, 95 % CI 0.28-0.77, p = 0.003) in OSA patients with hypertension. In contrast, the frequencies of ID (OR = 1.80, 95 % CI 1.08-2.99, p = 0.024) and DD genotypes (OR = 2.15, 95 % CI 1.30-3.57, p = 0.003) were significantly increased in this group. The activity of SACE was significantly decreased in the apneic group as compared to the non-apneic group (OR = 0.99, 95 % CI 0.98-1.00, p = 0.04). Conclusions: The findings suggest that II genotype confers susceptibility towards development of OSA whereas DD genotype confers susceptibility towards hypertension irrespective of OSA. [ABSTRACT FROM AUTHOR]

Background: According to the National Family Health Survey, asthma is one of the leading diseases in India. In order to understand the complexity of asthma, the susceptibility genes need to be targeted for their association. Glutathione S-transferases play a major role in the detoxification of metabolites of oxidative stress resulting in inflammation and asthma. In the present study, the hypothesis that GSTT1 and GSTM1 gene polymorphisms are associated with asthma was examined. Methods: This is the first study to investigate the role of GSTT1 and GSTM1 gene polymorphisms in asthma pathogenesis in a North Indian population. A total of 824 subjects were recruited, of which 410 were asthma patients, including 323 patients suffering from allergic rhinitis. The other 414 recruits were healthy controls from regions of North India. Multiplex PCR was used for genotyping the GSTT1 and GSTM1 gene polymorphisms. Results: The GSTT1 null allele was more prevalent in asthma patients (40 %) than in the control subjects (13.3 %), which yielded a nearly fourfold risk towards asthma with odds ratio (OR) (95 % CI) = 4.35 (3.04-6.24), χ = 75.34, and p = 0.000. The GSTM1 polymorphism also revealed a greater prevalence of the GSTM1 null allele in asthma patients (46.6 %) than in controls (39.4 %). Statistical analysis yielded a marginal risk toward asthma with OR (95 % CI) = 1.34 (1.01-1.79), χ = 4.37, and p = 0.036. Conclusions: Polymorphisms as a result of deletions in the GSTT1 and GSTM1 genes confer an increased risk towards asthma thereby suggesting the protective role of these functional genes in the development of the disease. [ABSTRACT FROM AUTHOR]

Background: β-Adrenergic receptor (βAR), a G-protein coupled receptor, is present on the bronchial smooth muscle cells and results in bronchodilation upon activation. The genetic factors determining βAR expression and function may not only alter the response of an individual to the therapy but also may serve as predictive markers for response to the agonists used in the therapy. The present study aimed at evaluating the role of βAR-16 and βAR-27 gene polymorphisms in asthma. Methods: A case-control study was performed with a total of 824 adult subjects, including 410 asthmatics and 414 healthy controls from regions of North India. The βAR-16 and βAR-27 polymorphisms were genotyped by PCR-RFLP. Results: Statistical analysis for the βAR-16 polymorphism revealed that the mutant Gly16 allele was significantly associated with asthma, with OR = 0.80, 95 % CI = 0.65-0.99, and P = 0.032. The Gly16/Gly16 mutant genotype also confers decreased risk toward asthma, with OR = 0.65, 95 % CI = 0.41-1.02, and P = 0.049. However, the βAR-27 polymorphism was not associated with asthma as it did not reach statistical significance, with OR = 0.86, 95 % CI = 0.69-1.07, and P = 0.163. Conclusion: The βAR-16 polymorphism confers a decreased risk toward asthma while the βAR-27 polymorphism is not associated with asthma in the studied North Indian population. [ABSTRACT FROM AUTHOR]

In this first report on the association of an IL- 10 promoter polymorphism with type 2 diabetes mellitus in a North Indian population, the −592A/C SNP (rs1800872) was genotyped by PCR-RFLP and the IL-10 level measured using ELISA. Although no significant difference was observed in the genotypic frequencies ( P = 0.657), diabetes patients carried a significantly higher number of A alleles at the −592 position, 25.6% ( P < 0.001, odds ratio 0.887, 95% CI 0.670-1.184). Significant correlations were detected in postprandial glucose levels of CC-genotype patients and controls ( P = 0.025), age and waist-hip ratio of CA patients and controls ( P ≤ 0.001), and fasting glucose ( P = 0.045) and low-density lipoprotein ( P = 0.049) in all patients and controls. The serum IL-10 level was significantly higher in patients than in controls ( P = 0.033). The polymorphism was significantly associated with disease incidence and its biochemical manifestations. [ABSTRACT FROM AUTHOR]

Nitric Oxide (NO) is an important molecule carrying number of different functions in humans. Published studies suggest that it may inhibit several key steps involved in the pathogenesis of atherosclerosis. Inhibition or reduction of NO due to Glu298Asp polymorphism may accelerate atherosclerosis. The aim of this study was to determine whether Glu298Asp polymorphism is implicated in the pathogenesis of coronary artery disease (CAD) among North Indian population from the state of Uttar Pradesh, India. We selected 253 CAD patients and 174 healthy, normotensive, non-diabetic controls, which were matched for gender and ethnicity. The Glu298Asp (rs1799983) variant was detected by genotyping subjects, using a polymerase chain reaction followed by restriction fragment length polymorphism. There was no significant difference found in the genotypic and allelic frequencies between patients and controls. Our study indicated that Glu298Asp polymorphism does not play any critical role in the pathogenesis of CAD, at least in North Indian population. [ABSTRACT FROM AUTHOR]

Humans are exposed to various environmental chemicals such as organochlorine pesticide residues, heavy metals, polychlorinatedbiphenyls (PCBs) etc. There is paucity of data regarding the present blood levels of organochlorine residues in North Indian population with reference to reproductive health. The present study was designed to analyze the levels of organochlorine pesticide residues in maternal and cord blood samples of normal healthy women with full term pregnancy to gain insight into the current status of pesticide burden in newborns. Hexachlorocyclohexane (HCH) contributed maximum towards the total organochlorine residues present in maternal and cord blood followed by endosulfan, pp′ DDE and pp′ DDT being the least. This is also the first report indicating endosulfan levels in this population. Our data indicates a transfer rate of 60–70% of these pesticides from mothers to newborns and this high rate of transfer of pesticides is of great concern as it may adversely affect the growth and development of newborn. [ABSTRACT FROM AUTHOR]