Forkhead box P3 gene polymorphisms predispose to type 2 diabetes and diabetic nephropathy in the Han Chinese populations: a genetic-associated and gender-based evaluation study

Abstract

Abstract Background Functional mutations or polymorphisms affecting FOXP3 could lead to abnormal FOXP3 gene expression and/or defective Treg cells generation, thus resulting in autoimmune disease and inflammation disorders, including type 2 diabetes mellitus (T2DM) and its complications, chronic and low-grade inflammatory disorders associated with long-term immune system imbalance. This study aimed to investigate the association of type 2 diabetes mellitus (T2DM) and type 2 diabetes nephropathy (T2DN) susceptibility with FOXP3 polymorphisms in the Han Chinese populations. Methods Polymorphisms of rs3761548C/A and rs2294021C/T were examined in 400 patients (including an equal number of T2DM and T2DN groups) and 200 healthy controls using PCR-HRM and sequence analysis. Conclusions Significant differences between the two SNPs in terms of genotype, allelic frequencies of T2DM, and progression of diabetes developing to T2DN. The further gender-based evaluation showed that, as for female subjects, rs3761548C/A was associated with around 3-fold higher hazards for T2DM and 4.5-fold for T2DN, respectively, while no noticeable association with rs2294021C/T; as for males, the promoter polymorphism showed an increased risk of 5.4-fold and 3.4-fold predisposition to T2DM and T2DN, respectively, and another polymorphism could impart a nearly 2-fold risk of developing T2DN. Additional analysis of combined genotypes revealed that CC-CC and CC-CT could be considered protective combinations in the predisposition towards T2DN among males with diabetes, while AA-CC and AA-TT did the opposite effect. Results This study provides the first evidence for the genetic association of rs3761548C/A and rs2294021C/T polymorphisms with the susceptibility to diabetes and diabetic nephropathy in the Han Chinese population, as well as assessing gender differences.