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Hyperglycemia plays a pronounced role in accelerating the process of aging due to high oxidative stress which triggers dyslipidemia and subsequently led to the progression of cataract. The aim of this study was to investigate lipid profile and its relationship with genotypes of SOD1, GPX1, and CAT variants in cataract patients. Total n = 680 samples were screened in four groups: senile cataract (SC), diabetic cataract (DC), type 2 diabetes mellitus (DM), and controls (CL). Lipid profile was estimated and compared between groups, and its correlation was tested with glycemic markers. Association of SOD1 50 bp Indel, GPX1 (rs1800668), and CAT (rs1001179) genotypes with all clinical variables was investigated in cataract groups by regression statistics in SPSS® 16.0. Comparative analysis revealed that amount of total cholesterol and low-density lipoprotein parameters were significantly higher in both groups of cataracts when compared with controls (p 0.01). Statistically higher levels of triglycerides were also evident in DM patients as compared with other three groups (p 0.01). Significant weak positive correlation of glycated hemoglobin, fasting (FBG), and random blood glucose (RBG) levels was observed with triglycerides in DM (r = 0.16), SC (r = 0.15), and DC (r = 0.18) groups. Mutant genotype of SOD1 and CAT variants indicated significant association with TC, whereas GPX1 variant with FBG levels in accelerating predisposition of cataract in patients with diabetes (OR 1.0). Outcomes suggested that TG may serve as a potential biomarker of lipid profile with manifestation of cataract in type 2 DM. Furthermore, hypercholesterolemia and hypertriglyceridemia demonstrated an inducing role in the pathogenesis of cataract with aging in hyperglycemia.

Cataract formation is accelerated by hyperglycemia due to the excessive production of oxidative stress. This study aimed to examine the underlaying role of glutathione peroxidase 1 (GPX1) rs1800668, catalase (CAT) rs1001179 and superoxide dismutase 1 (SOD1) 50 bp Indel promotor region variants in the pathogenesis of cataract in patients with diabetes.A population-based case-control study of n=680 individuals was conducted which comprised of four respective groups: type 2 diabetes mellitus, diabetic cataract, senile cataract patients and controls. Screening of genotypes was performed by allele-specific (AS) and conventional polymerase chain reaction (PCR). Statistical testing was carried out using SPSS© 20.0, MedCal© and SNPStats© software's. Bioinformatics analysis of linkage disequilibrium was done by HaploView© software 7.0.GPX1 (rs1800668) showed significant association with higher susceptibility of opacification in type 2 diabetes mellitus (χGPX1 (rs1800668) variant may serve as an antioxidant biomarker for the assessment of risk for cataract in type 2 diabetes mellitus. GPX1 enzyme owed an antioxidant activity which can reduce the oxidative stress and hence could develop resistance in cataractogenesis. The findings could be beneficial as a potential target to the future pharmacogenomic studies of cataract prevention and eradication in diabetes mellitus.

Introduction: Oxidative stress plays an essential role in the pathogenesis of type 2 diabetes mellitus (T2DM). An antioxidant enzyme superoxide dismutase 1 (SOD1) dissociates free superoxide radicals and provides protection against oxidative damage. The aim of this study was to investigate the role of promotor region 50 bp Indel SOD1 polymorphism with the pathogenesis of type 2 diabetic mellitus among Pakistani population. Materials and Methods: This was a case-control study comprised of n=359 subjects, divided into n=178 type 2 diabetic patients and n=181 controls. Screening of SOD1 promotor 50 bp Indel polymorphism was carried out by conventional polymerase chain reaction (PCR). Statistical interpretations were done by software SPSS® version 20.0 and SNPStats©. Results: Genotype distribution pattern of SOD1 polymorphism indicated that homozygous mutant D/D genotype frequency was two folds reduced in T2DM (0.01) in comparison to controls population (0.02). Heterozygous I/D genotype frequency was higher in T2DM subjects (0.22) as compared to controls (0.17). An insignificant association of SOD1 polymorphism was detected with predisposition of T2DM (OR=1.14, Fisher’s exact=2.0, p=0.325). Genetic analysis further revealed that dominant model showed significant association against the pathogenicity of disease (OR=0.45, p

Aim/background To assess the effectiveness of mobile SMS as a tool for behavior and life style modification in management of diabetes. Methods This interventional study was conducted from July 2014 to April 2015 at Baqai Institute of Diabetology and Endocrinology (BIDE). Demographical and clinical information of subjects (patients and relatives) along with their knowledge and beliefs regarding diabetes was recorded using questionnaire. In Short Message Service (SMS) and non-SMS groups, education regarding diabetes was given. Two messages per day were sent to SMS group for two months. Results Total 648 subjects, SMS (n = 376) and non-SMS (n = 276) groups, were included in study. Mean age of patients and relatives was 45.41 ± 15.13 and 34.58 ± 11.91 in SMS group, while 47.06 ± 14.83 and 31.02 ± 11.51 in non-SMS group, respectively. No significant difference regarding level of knowledge and beliefs among both groups was observed at baseline. After SMS intervention, level of knowledge (p ≤ 0.0001) and beliefs (p ≤ 0.0001) were found to be significantly higher in SMS groups Non-SMS group. Conclusion Mobile SMS are an effective tool to deliver behavior and lifestyle modification advice and support for better management of diabetes and its prevention in people who are at high risk. Education intervention through SMS is found to be an important variable which enhances the knowledge and beliefs of the subjects.

BACKGROUND Coronary artery disease (CAD) is a leading cause of mortality in Pakistan and also worldwide. Vitamin D receptor (VDR) regulates the transcription of many genes and has a significant impact on inflammation and the morphology of cardiac cells. Genetic variation in the VDR gene such as the TaqI polymorphism (rs731236) may have an impact that causes adverse effects. Accordingly, it is important to determine possible association of the TaqI polymorphism (rs731236) with CAD. METHODS The study included blood samples from 1016 subjects: 516 from CAD patients and 500 from age- and gender-matched controls. Genomic DNA was extracted by standard salting out method. Targeted variation was amplified by an allele-specific polymerase chain reaction (PCR). PCR products were examined and genotyped on agarose gel electrophoresis represented by an amplified product size of 148 bp followed by Sanger sequencing to validate variations. RESULTS Serum vitamin levels, as observed using enzyme-linked immunosorbent assay, were found to be insufficient in both CAD patients (20.52 ± 0.06 ng/ml) and controls (21.6981 ± 0.05 ng/ml). The TaqI polymorphism (rs731236) T>C was found to be significantly associated with CAD (p

Aim To determine the effect of genetic variants within the FTO gene (rs9939609) on obesity related traits and type 2 diabetes in South Asian population of Karachi, Pakistan. Methods A case-control study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University situated in Karachi. A total of 296 patients with known type 2 diabetes and 198 controls aged greater than and equal to 45 years were recruited. The Anthropometric, clinical and biochemical data was collected on a structured questionnaire. Single nucleotide polymorphism (SNP) in FTO gene was identified by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Association between the single nucleotide polymorphism and categorical variables such as type 2 diabetes and obesity category was tested through logistic regression analysis. Results We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes. Significant difference was observed in frequency of FTO genotype when diabetic subjects were compared with controls in co dominant, dominant and recessive models. This association remained significant even after adjusting for body mass index (BMI) and for waist circumference. The frequency of homozygous risk Alleles (AA) was found to be higher in obese & overweight (≥23 kg/m 2 ) and females with central obesity in our study population. The association of FTO variant with BMI and central obesity does not reach to statistical significance. Conclusion In the study population of South Asian ancestry, variants of the FTO gene predispose to type 2 diabetes, but not entirely through their effect on BMI.

Background & Objective: Catalase (CAT) is an important endogenous antioxidant enzyme that detoxifies H2O2 into water and oxygen, consequently limiting the deleterious effects of reactive oxygen species. It has suggested that CAT-21A/T (rs7943316) OMIM: 115500 gene promoter polymorphism is predominantly associated with different human disorders such as hypertension, cancers, diabetes, nephropathy, and other diseases accompanied by oxidative stress. This study was designed to investigate the prevalence of mutant T allele frequency in healthy individuals. Methods: The study group consisted of 110 healthy individuals were enrolled from Baqai Institute of Diabetology and Endocrinology (BIDE), Karachi, Pakistan, during the period of April 2010 to May 2013. DNA was isolated from leukocytes. Genotyping of CAT-21A/T (rs7943316) gene promoter polymorphism was carried out using thermal cycler followed by RFLP. Blast N analysis was performed for the confirmation of gene sequences. Results: In CAT-21A/T (rs7943316) gene promoter polymorphism, wild type genotype (AA) was observed in 18.26% and alterered genotype (AT/TT) found in 81.74% cases. Conclusions: Data demonstrates that frequency and distribution of mutant T allele was more prevalent as compared to wild type A allele in the study group.

Diabetes mellitus (DM) is a chronic metabolic syndrome that can lead to serious vascular complications. Diabetic nephropathy (DN) has been established as the leading cause of deaths in diabetes due...

Diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic and retinal complications. Diabetes clustered with hypertension and nephropathy has become the leading cause of end-stage renal disease globally. This study describes diabetes, hypertension and nephropathy with reference to glycemic control, dyslipidemia and endothelial dysfunction indicating the foremost basis of morbidity and mortality world wide and rapidly progressing in Pakistan. Study subjects selected and divided in four groups (60 each) followed by institutional ethical approval and informed consent. Group 1: non-diabetic, normotensive control subjects; Group 2: diabetic, normotensive patients; Group 3: diabetic, hypertensive patients and Group 4: diabetic, hypertensive patients with nephropathy. Their fasting blood samples analyzed for the estimations of blood glucose, HbA1c, serum triglyceride, cholesterol, LDL-cholesterol, HDL-cholesterol, urea, creatinine, nitric oxide and sialic acid levels. Results showed that all the groups showed significant rise in fasting blood glucose. Similarly HbA1c levels were also significantly high in all the patients as compared to controls. Group 2 showed significantly high serum cholesterol and LDL levels and low HDL levels. Group 3 and 4 showed significantly high serum triglyceride, cholesterol and LDL levels where as low HDL levels as compared to controls. Group 3 showed significantly high serum creatinine. Group 4 showed a significantly high serum urea and creatinine as compared to controls. Persistent albuminuria was characteristic in Group 4 patients. Significantly low production of serum nitric oxide with high concentration of serum sialic acid was observed in Group 3 and 4 as compared to controls. Results indicate a clear relationship of declining renal function with poor glycemic control, abnormal lipid metabolism, endothelial dysfunction and initiation of acute phase response in tissues affected from the microvascular complications of diabetes like hypertension and nephropathy. It must be taken into account while screening diabetic patients to get them rid of progressive renal impairment leading to end stage renal disease.

Background: The extracellular matrix protein 1 (ECM1) is a glycoprotein, expressed in skin and other tissues. Loss-of-function mutation in ECM1 causes a rare autosomal recessive disorder called lipoid proteinosis. Lipoid proteinosis is presented by varying degrees of skin scars, beaded papules along the eyelid margins, variable signs of hoarseness of voice and respiratory disorders. More than 250 cases of this disorder have been described in the literature, but occurrence of lipoid proteinosis in siblings is very rare. This study was designed to investigate the possible mutation causing lipoid proteinosis in a Pakistani family and to elaborate the scope of possible genetic changes, causing the genodermatosis in Pakistan. Main observations: In this study, two siblings (12 and 9-years sisters) were presented with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother and younger brother were unaffected. Blood samples from clinically affected and unaffected family members were collected with informed consent. The coding region of ECM1 gene containing 10 exons were amplified and sequenced. Both the affected siblings were shown to have homozygous frame shift mutation by deletion of the nucleotide T at 507, codon 169, exon 6. This resulted in a frame shift from codon 169 and appearance of a premature stop codon at 177, causing formation of a mutated protein (176 amino acids) instead of normal ECM1 protein (540 amino acids). Conclusion: A case of homozygous 62-bp insertion in ECM1 gene causing lipoid proteinosis has been reported in another Pakistani family. The current study presents a homozygous frame shift mutation supporting an unusual function of ECM1 protein and broadens the spectrum of disease-linked mutations in this rare case of genodermatosis in this region. ____________________________________________________ Samdani AJ, Azhar A, Shahid SM, Nawab SN, Shaikh R, Qader SA, Mansoor Q, Khoso BK, Ismail M. Homozygous frame shift mutation in ECM1 gene in two siblings with lipoid proteinosis. J Dermatol Case Rep. 2010; 4(4): 66-70.

A number of mutations in extracellular matrix protein 1 (ECM1) that is a glycoprotein and expressed in skin and other tissues are reported to cause a rare, autosomal recessive disorder called lipoid proteinosis (LP). The peculiar manifestation of LP is hoarseness of voice caused by laryngeal infiltration in infancy. Skin and mucous membrane changes clinically become apparent, and the disease typically follows a slowly progressive, yet often benign, course. About 300 cases of LP have been reported, but occurrence in siblings is rare. In this study, two siblings (18 and 24-year-old) of a Pakistani family were reported to have LP. This study presents two brothers with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother, younger brother and sister were unaffected. Blood from affected and clinically unaffected family members were collected with informed consent. The ECM1 gene containing 10 exons were amplified and sequenced. Both patients showed non-pathogenic missense and silent mutations in exon 6 and 8. In exon 6, a nucleotide C was substituted to T (C→T) at codon 2, in patient 1. This nonpathogenic missense mutation causes appearance of amino acid cysteine instead of arginine that is part of normal ECM1 protein. In patient 2, polymorphism of nucleotide C to T (C/T) was observed observed in exion 6 that may lead to the appearance of cysteine and/or arginine in the resulting gene product. In exon 8, a nucleotide G was substituted to A (G→A) at codon 53, in patient 1. This substitution leads to a silent mutation as serine is coded by both forms of codon. In patient 2, polymorphism of nucleotide G to A (G/A) was observed in exion 8 that do not cause any change in the coded amino acid. These findings represent a set of missense and silent mutations supporting an unusual function of ECM1 protein, broadening the spectrum of disease-linked mutations in rare cases of LP. Key words: Lipoid proteinosis, extracellular matrix protein 1 (ECM1), missense, silent mutation, single nucleotide polymorphism, exons 6 and 8, genodermatosis.