SNPs in PRKCA-HIF1A-GLUT1 are associated with diabetic kidney disease in a Chinese Han population with type 2 diabetes

Abstract

Objective: To explore the relationship between SNPs in PRKCA-HIF1A-GLUT1 and diabetic kidney disease in Chinese Han people.

Materials and methods: A total of 2552 participants from Shanghai Diabetes Institute Inpatient Database of Shanghai Jiao Tong University Affiliated Sixth People's Hospital were involved in the stage 1 cross-sectional population. A total of 6015 subjects from the Hong Kong Diabetes Register were included for validation. Genotyping of participants was conducted by the MassARRAY Compact Analyzer (Agena Bioscience). The data were analysed by plink, SAS, Haploview.

Results: We identified variants associated with diabetic kidney disease in stage 1. Rs1681851 (P = .0105, OR = 1.331) in GLUT1 as well as rs2301108 (P = .0085, OR = 1.289) and rs79865957 (P = .0204, OR = 1.263) in HIF1A were significantly associated with diabetic kidney disease. Regarding DKD-related traits, rs1681851 was associated with plasma creatinine levels (P = .0169, β = 4.822) and eGFR (P = .0457, β = -6.956). Moreover, the results showed the interactions between PRKCA-GLUT1 in the occurrence of DKD. We further sought validation of the 17 SNPs in a prospective cohort and found that rs900836 and rs844501 were associated with the percentage change in eGFR slope. We performed a meta-analysis of case-control analysis data from the Hong Kong samples together with the stage 1 data from Shanghai. Rs9894851 showed significant correlation with the serum creatinine level as well as eGFR and no SNP showed association with DKD after meta-analysis.

Conclusions: Our results suggest potential association between SNPs in PRKCA-HIF1A-GLUT1 and diabetic kidney disease in Chinese Han people.

Keywords: GLUT1; HIF1A; PRKCA; SNP; diabetic kidney disease; type 2 Diabetes.