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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 < 0.0001). The odds ratio showed that the risk increases by 1.8-fold with variant C allele. Dominant, co-dominant and over dominant genetic model analyses suggested that the TC genotype might be a risk factor involved in the possible association with susceptibility to CAD. Conclusions:The TaqI polymorphism (rs731236) in the coding region may affect the function of the receptor by altering the binding site, which might participate in an inflammatory response and increase the risk for developing susceptibility to CAD.

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.

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.

. The present study is based on a previously published case-control study that indicates the association of different FTO gene with type 2 diabetes. The structured questionnaire was used to gather anthropometric, biochemical, and clinical data. Single nucleotide polymorphism (SNP) in FTO gene was analyzed using Amplication Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). The nutritional data were collected using a 24-hour dietary recall questionnaire completed by a trained dietitian. The variations in energy and macronutrient intake of subjects having different FTO gene alleles were investigated and evaluated for correlations between energy and macronutrient intake and metabolic risk variables in three FTO-gene-allele groups. Results: Overall, 198 adult subjects with type 2 diabetes (T2D) were recruited and categorized into three genotype groups: TT, AA and AT with the mean age of 49.7 ±9.7, 49.3 ±10.6 and 50.2 ±8.8 years, respectively. A close association was observed between the minor allele A at rs9939609 and type 2 diabetes. A linear correlation was observed between diet and metabolic prole markers such as BMI, waist circumference, blood pressure, and lipid prole among high-risk alleles AA. The associations of energy intake and percent level of carbohydrate and protein intake with metabolic syndrome were signi-cantly higher among risk alleles AA (P<0.05). However, the majority of the biochemical parameters and dietary components were found to be statistically insignicant (p>0.05). Discussion: Genetic prole is likely to affect both dietary habits as well as the association between diet and metabolic syndrome markers. This study concludes that diet-disease associations are more prominent in individuals having risk alleles AA as compared to protective alleles TT and heterozygous alleles AT. Keywords: Diet, T2DM, FTO, nutrigenomicsAmaç: Farklı FTO gen alellerine sahip Tip 2 diyabetli bireylerde çeşitli gıda alımının metabolik risk belirteçleri üzerindeki etkisini değerlendirmek. Gereç ve Yöntemler: Çalışma, Mart 2011 ile Mayıs 2013 arasında Baqai Diabetoloji ve Endokrinoloji Enstitüsü (BIDE) Karachi, Pakistan'da gerçekleştirildi. Bu çalışma, farklı FTO genlerinin Tip 2 diyabet ile ilişkisini gösteren önceden yayımlanmış bir vaka kontrol çalışmasına dayanmaktadır. Antropometrik, biyokimyasal ve klinik verileri toplamak için yapılandırılmış anket kullanılmıştır. FTO genindeki tek nükleotid polimorzmi (SNP), Amplikasyon Refrakter Mutasyon Sistemi-Polimeraz Zincir Reaksiyonu (ARMS-PCR) kullanılarak analiz edildi. Beslenme verileri, eğitimli bir diyetisyen tarafından doldurulmuş 24 saatlik bir diyet hatırlatma anketi kullanılarak toplandı. Farklı FTO gen alellerine sahip bireylerin enerji ve makro besin alımındaki değişiklikler araştırıldı ve üç FTOgen-alel grubundaki enerji, makrobesin alımı ve metabolik risk değişkenleri arasındaki korelasyonlar açısından değerlendirildi. Bulgular: Genel olarak, Tip 2 diyabetli (T2D) 198 erişkin hasta çalışmaya alındı ve üç genotip grubuna ayrıldı: yaş ortal...