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Type 2 diabetes mellitus (T2DM) is an increasingly common metabolic disorder with a substantial inherited component. The inheritance pattern is complex and polymorphisms of several genes might influence genetic susceptibility of the disease that is characterized by islet dysfunction and insulin resistance. Although various characteristics of diabetes mellitus in local population have been investigated, progress in defining genetic factors is meager. As the genetic architecture of T2DM may vary between diverse ethnic populations, it is critical that such variants are examined in Pakistani population. The present project was aimed to investigate association of vitamin D receptor(VDR) gene polymorphisms with T2DM in Pakistan. Methodolgy included documentation of demographic charateristics and comparative analysis of biochemical parameters (glucose, HbA1c, vitamin D, lipid profile, liver function tests and renal function tests)in diabetic and normal participants. Genomic DNA was used for genotyping of four restriction fragment length polymorphism (RFLP) sites; BsmI, ApaI, TaqI and FokI by polymerase chain reaction (PCR) amplifications and restriction endonuclease digestion of the products. The digested PCR products were separated on agarose gel electrophoresis. Among all the demographic parameters, systolic and diastolic blood pressure and BMI (body mass index) were significantly higher (p<0.001) in diabetic group as compared to the control group. Hyperglycemia, renal and lipid profiles were significantly inversely associated (p<0.01) to vitamin D levels in T2DM subjects.Differences of FokI, BsmI and TaqI genotypes of VDR gene were significant between T2DM and normal groups (p<0.01).While ApaI showed non-significant association to the T2DM in local population. No significant association was found between biochemical parameters and all four restriction sites (ApaI, BsmI, FokI and TaqI) (p>0.01). In addition, VDR gene polymorphisms were related non-significantly (p>0.05) to the diabetic complications in the present study. To conclude, VDR gene polymorphisms (BsmI, FokI and TaqI) may contribute to the onset and progression of T2DM in local Pakistani population but association between VDR genetic polymorphisms to various diabetic complications is still not clear and warrants additional functional genomics studies to verify the genetic susceptibility of VDR gene to T2DM onset and progress.
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