EVALUATION OF CLINICAL SIGNIFICANCE OF SIRT-1 GENE SINGLE NUCLEOTIDE POLYMORPHIMS WITH TYPE2 DIABETES MELLITUS AND ITS COMPLICATION IN NORTH WESTERN RAJASTHAN: A CROSS SECTIONAL STUDY: Research Article

balkishan gupta

doi:10.58372/2835-6276.1042

Authors

balkishan gupta

DOI:

https://doi.org/10.58372/2835-6276.1042

Abstract

Introduction: The environmental and genetic factors are involved in the pathogenesis of T2DM. Genetic polymorphisms that have impacts on important proteins which participate in glucose metabolism and insulin secretion may also affect susceptibility to T2DM. SIRT1 gene have been shown to play pivotal roles in the regulation of ageing, longevity and in the pathogenesis of age-related metabolic diseases, such as type 2 diabetes mellitus. The aim of the current study was to investigate possible correlations between genetic variation in the SIRT1 gene and related clinical traits of T2DM.

Material and Methods: This was a cross sectional study conducted in Department of Medicine, S.P. Medical College, Bikaner on 60 previously diagnosed type 2 diabetes mellitus patients (study group) and compare them with 30 healthy subjects (control group). All subjects were evaluated by detail history and clinical examination as per Performa. Laboratory investigation CBC, RFT, LFT, fasting and two hours post prandial blood glucose, HbA1c and Lipid profile were done in all subjects. Fundus.examination, urine microalbuminuria and clinical examination for touch sensation with 10gm monofilament, vibration sense by biothesiometer and ankle reflex was done in all cases to find Diabetic complications.

Result: The mean age of diabetic subjects was 53.33±11.56 years and that of non-diabetic 56.6±11.27. We found significant association of single nucleotide polymorphisms (SNPs) with diabetes. SIRT1 rs10509291 polymorphism was positive in 70% cases of diabetes and 40% control subjects, SIRT1 rs3758391 polymorphism was positive in 33.33% of diabetes and 13.33% control subjects (p-value 0.0065 and 0.043 respectively). We observed that odds ratio was more than one for age, BMI, total cholesterol, triglycerides, VLDL, HbA1c and calorie intake but statistical significance (p-value<0.05) was found only with triglycerides, VLDL, and calorie intake. SIRT1 rs10509291 and SIRT1 rs3758391 gene polymorphism was associated with nephropathy (p-0.035 and 0.025 respectively), SIRT1 rs10509291 gene polymorphism with presence of retinopathy (p<0.0003) and SIRT1 rs3758391 gene polymorphism with neuropathy (p<0.0253).

Conclusion: We observed a statistically significant single nucleotide polymorphisms of SIRT1 rs10509291 and SIRT1 rs3758391 with type 2 diabetes mellitus and diabetic nephropathy. We also observed a statistically significant single nucleotide polymorphisms of SIRT1 rs10509291 with diabetic retinopathy and single nucleotide polymorphism of SIRT1 rs3758391 with diabetic neuropathy. Further large scale, multinational, multicentric studies are required to document significance of SIRT1 polymorphism so as to develop therapeutic target for prevention of diabetes and its complications.

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