Variants in PPARD-GLP1R are related to diabetic kidney disease in Chinese Han patients with type 2 diabetes mellitus.

Genetic susceptibility is an important pathogenic mechanism in diabetic kidney disease (DKD). Our previous studies have identified that PPARδ and GLP-1R are located in a pathway that is closely related to DKD. We aimed to explore the impacts of variants in PPARD-GLP1R on the susceptibility to DKD in Chinese Han patients with type 2 diabetes mellitus (T2DM). A total of 600 T2DM patients (300 with DKD and 300 without DKD) and 200 healthy control subjects were enrolled to identify PPARD (rs2016520, rs2267668 and rs3777744) and GLP1R (rs3765467, rs1042044 and rs9296291) genotype. The SNaPshot method was used to identify variants in PPARD-GLP1R. We performed correlation analysis between variants in PPARD-GLP1R and the susceptibility to DKD. We observed that GLP1R rs3765467 (G > A) was associated with DKD (OR = 3.145, 95 % CI = 2.128-6.021, P = 0.035). None of the other SNPs were associated with DKD. Regarding DKD related traits, rs3765467 was associated with UACR levels and TC, significant differences were observed among patients with different genotypes of rs2016520 in terms of BMI and TG, and patients with the rs3777744 risk G allele had noticeably higher PPG and HbA1c levels (P < 0.05). Moreover, the results showed the interactions between PPARD rs3777744 and GLP1R rs3765467 in the occurrence of DKD (OR = 4.572, P = 0.029). The results of this study indicate the potential relationship between variants in PPARD-GLP1R and the susceptibility to DKD in Chinese Han patients with T2DM.