National Clinical Research Center of Kidney Diseases, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Jiaotong University affiliated 6th People's Hospital, Shanghai, China.
Eur J Clin Invest. 2020 Sep;50(9):e13264. doi: 10.1111/eci.13264. Epub 2020 May 29.
To explore the relationship between SNPs in PRKCA-HIF1A-GLUT1 and diabetic kidney disease in Chinese Han people.
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.
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.
Our results suggest potential association between SNPs in PRKCA-HIF1A-GLUT1 and diabetic kidney disease in Chinese Han people.
探讨中国汉族人群中 PRKCA-HIF1A-GLUT1 单核苷酸多态性与糖尿病肾病的关系。
本研究纳入了来自上海交通大学附属第六人民医院上海糖尿病研究所住院数据库的 2552 名参与者进行了 1 期横断面人群研究，同时纳入了来自香港糖尿病注册中心的 6015 名参与者进行了验证。采用 MassARRAY Compact Analyzer（Agena Bioscience）对参与者进行基因分型。采用 plink、SAS、Haploview 进行数据分析。
我们在 1 期研究中发现了与糖尿病肾病相关的变异。GLUT1 中的 rs1681851（P=0.0105，OR=1.331）以及 HIF1A 中的 rs2301108（P=0.0085，OR=1.289）和 rs79865957（P=0.0204，OR=1.263）与糖尿病肾病显著相关。在与 DKD 相关的特征方面，rs1681851 与血浆肌酐水平（P=0.0169，β=4.822）和 eGFR（P=0.0457，β=-6.956）显著相关。此外，结果显示 PRKCA-GLUT1 之间存在相互作用，导致 DKD 的发生。我们进一步在前瞻性队列中对 17 个 SNP 进行了验证，发现 rs900836 和 rs844501 与 eGFR 斜率的百分比变化相关。我们对来自香港样本的病例对照分析数据和上海的 1 期数据进行了荟萃分析。rs9894851 与血清肌酐水平以及 eGFR 显著相关，荟萃分析后没有 SNP 与 DKD 相关。
我们的研究结果表明，中国汉族人群中 PRKCA-HIF1A-GLUT1 单核苷酸多态性与糖尿病肾病之间存在潜在关联。
