Lifestyle Modifications on the Expression of TCF7L2 Gene Polymorphism: A Cross-sectional Study

Abstract

Introduction: Type 2 Diabetes Mellitus (T2DM) is the result of the clustering of factors along with the communication between environmental factors and a strong hereditary component. In this modern age of investigation, molecular mechanisms of Transcription Factor 7 Like 2 (TCF7L2) linking with the physiological functioning in pancreatic and intestinal endocrine cells are explored. Hitherto few studies have been done in the Indian population with regard to gene polymorphism in TCF7L2 and T2DM concerning family history. Aim: To study effect of lifestyle modifications on the expression of TCF7L2 gene polymorphism in subjects with family history of diabetes. Materials and Methods: This was a cross-sectional study, conducted over a period of 14 months September 2020 to November 2021) with 121 subjects from Shimoga district at Shimoga Institute of Medical Sciences, Shivamogga, Karnataka, India. The study was conducted after the approval by the Ethics Committee and subjects volunteering for the study have signed the informed consent. The study comprised of two groups. Both the groups had family history of T2DM, eventually persons who had not developed diabetes and had changed their lifestyle were grouped I (n=56) and subjects who had developed diabetes without any changes in their lifestyle were considered as group II (n=65). Fasting insulin, and fasting blood glucose was estimated along with the anthropometric variables like height, weight, waist circumference, hip circumference. Two Single Nucleotide Polymorphism (SNP) (rs7903146 and rs1225372) of TCF7L2 gene was genotyped using Tetra-primer Amplification Refractory Mutation System (T-ARM) protocol. Differences in clinical parameters and genotypic variants between groups, was calculated using the independent t-test and Chi-square test, a p value of <0.05 was considered statistically significant. Results: Only fasting insulin and WHR Waist Hip Ratio (WHR) parameters were weakly significant in the study population. The risk allele frequency (T) was seen to be higher in the group I and the chances of getting diabetics was 2.02 times higher than the subjects of group II for rs7903146. This substantiates that the group I subjects were more predisposed to diabetes genetically. Since subjects with heterozygous genotype (CT or GT alleles) has been associated with the highest risk of developing T2DM, the association of heterozygous genotype was high in the group with lifestyle modification and was highly significantly associated with risk of being diabetic by 7.50 times for rs7903146 and 6.10 times for rs1225372. Further risk analysis of variants according to a model of inheritance was analysed and was observed that the co-dominant and overdominant models best fitted the association with an OR above 6 for both the polymorphism. Conclusion: This study depicts that lifestyle modification masks the effect of risk variants for rs12255372 and rs7903146. The confounding nature of the influence of environmental factors over predisposition to inheritance is well depicted for the manifestation of T2DM among the genetic variants of TCF7L2.