Association of Vitamin D Receptor Gene G>T And T>C Polymorphisms in The Pathogenesis of Impaired Glucose Tolerant Subjects of Bangladesh

Abstract

Vitamin D receptor (VDR) gene polymorphisms have been found to be associated with pancreatic B cell secretion and glucose intolerance. The present study was undertaken to determine genotype of VDR gene Apa1 (G>T) and Taq1 (T>C) polymorphism of a group of impaired glucose tolerance (IGT) subjects of Bangladeshi origin and investigate its association with its insulin sensitivity and cell secretory capacity. A total number of 54 IGT subjects were recruited in the study and 68 healthy subjects served as control. Oral glucose tolerance test was performed and IGT was diagnosed following WHO Guidelines. Blood glucose was measured by glucose-oxidase and, triglyceride, total cholesterol and HDL-cholesterol by enzymatic colorimetric method. Insulin was estimated by enzyme linked immunosorbent assay (ELISA), and insulin secretory capacity (HOMA%B) and sensitivity (HOMA%S) were determined using HOMA-Sigma Software. DNA was isolated using QIAGEN Blood DNA Kit which utilizes silica gel DNA separation. VDR gene variants [G>T and T>C] were analyzed by PCR-RFLP using restriction enzymes Apa1 and Taq1 respectively. Data were managed using Statistical Program for Social Science (SPSS) for Windows version 10. Unpaired Student’s-‘t’ test and Chi-squared tests were performed where appropriate. Circulatory insulin level was found to be higher (p<0.001) and reflected in their lower insulin sensitivity (as judged by HOMA%S) level (p=0.003). The G>T genotypes frequencies in the control and IGT were 0.176, 0.618, 0.206 (wild, heterozygous variants and homozygous variants respectively) and 0.185, 0.537, 0.278 respectively. The T>C genotypes frequencies were in the control were 0.500, 0.456, 0.044 (wild, heterozygous variants and homozygous variants respectively) and IGT 0.444, 0.426, 0.130 respectively. Genotypes frequencies of G>T and T>C did not show significant association with IGT (p=0.606 and 0.230 respectively). Wild and Variant genotypes of the two marker allele did not show significant difference regarding glucose level (fasting and 2 hour postprandial) and insulinemic status (insulin, HOMA%B and HOMA%S) either in Controls or IGT subjects. It was concluded that i) VDR gene Apa1 (G>T) and Taq1 (T>C) polymorphic alleles are not associated with IGT of Bangladeshi origin; (ii) The polymorphic marker alleles did not have any effect on fasting and two hour blood glucose and insulinemic status of the IGT and Controls; and (iii) The data reconfirmed that lower insulin sensitivity is predominantly present in the IGT subjects of Bangladeshi origin.