Association Between ABCG1/TCF7L2 and Type 2 Diabetes Mellitus: An Intervention Trial Based on a Case-Control Study.

Background and Objective: Type 2 diabetes mellitus (T2DM) is the result of both genetic and environmental factors. Environmental factors may contribute to the occurrence and development of T2DM by influencing epigenetic modification. The objective of this study was to explore the potential functions of two SNP-CG sites (rs7901695 of TCF7L2 and cg06500161 of ABCG1) that are most strongly associated with T2DM. Given that Uyghur population has been less studied, we conducted an intervention trial in Uyghur people to provide evidence for personalized health management of T2DM in them. Methods: From May to July 2022, 320 patients with T2DM and 332 patients without T2DM were treated with dietary pagoda-based health education intervention. The demographic data were collected before intervention and basic physical biochemical indexes before and after intervention by questionnaire and physical biochemical examination. SNP typing was performed by the TaqMan-MGB probe method, and gene methylation was detected by the pyrosequencing method. Results: The rs7901695 genotype difference of TCF7L2 was statistically significant between the case group and the control group (p < 0.05). After adjusting for covariates (smoking, alcohol consumption, exercise, fasting blood glucose (FPG), obesity, and hypertension), the genotype of rs7901695 in the TCF7L2 gene was associated with genetic susceptibility to T2DM in additive (TC vs. TT,p = 0.047; CC vs. TT,p = 0.010), dominant (p = 0.015), and recessive (p = 0.039) models. Before intervention, there were significant differences in the intake of water between the case group and the control group (p < 0.05). After intervention, there was statistical significance in the intake of coarse grains, fruits, aquatic products, eggs, dairy products, soy products, nuts, edible oils, and water between the case group and the control group (ps < 0.05). Logistic regression analysis showed that methylation of the ABCG1 gene was correlated with T2DM susceptibility after adjustment of covariable before intervention (p = 0.015, odds ratio (OR): 1.023; 95% confidence interval (CI): 1.004~1.041) but not after intervention. Generalized multifactor dimensionality reduction (GMDR) showed that the rs7901695 locus of the TCF7L2 gene and the cg06500161 locus of the ABCG1 gene had interaction with hypertension, dyslipidemia, abdominal obesity, and obesity and also had interaction with drinking, smoking, and exercise. Conclusions: The interaction of the rs7901695 site of the TCF7L2 gene and the cg06500161 site of the ABCG1 gene with environmental factors may increase the risk of T2DM in Uyghurs. The interaction between the cg06500161 site of the ABCG1 gene and environmental factors on T2DM varied with the intervention. The cg06500161 site of ABCG1 may serve as a biomarker to evaluate the effect of T2DM interventions.