GCKR and GCK polymorphisms are associated with increased risk of end-stage kidney disease in Chinese patients with type 2 diabetes: The Hong Kong Diabetes Register (1995–2019)

Abstract

AimsGlucokinase (GCK) and glucokinase regulatory protein (GKRP) regulate glucose and lipid metabolism. We investigated the associations of GCKR and GCK polymorphisms with kidney outcomes. MethodsAnalyses were performed in a prospective cohort who were enrolled in the Hong Kong Diabetes Register between 1995 and 2017. The associations of GCKR rs1260326 and GCK rs1799884 polymorphisms with incident end-stage kidney disease (ESKD), albuminuria and rapid eGFR decline were analysed by Cox regression or logistic regression with adjustment. Results6072 patients (baseline mean age 57.4 years; median diabetes duration 6.0 years; 54.5 % female) were included, with a median follow-up of 15.5 years. The GCKR rs1260326 [HR (95 %CI) 1.23 (1.05–1.44) for CT; HR 1.23 (1.02–1.48) for TT] and GCK rs1799884 T alleles [HR 1.73 (1.24–2.40) for TT] were independently associated with increased risk of ESKD versus their respective CC genotypes. GCKR rs1260326 T allele was also associated with albuminuria [OR 1.18 (1.05–1.33) for CT; OR 1.34 (1.16–1.55) for TT] and rapid eGFR decline. ConclusionsIn Chinese patients with type 2 diabetes, T allele carriers of GCKR rs1260326 and GCK rs1799884 were at high risk for ESKD. These genetic markers may be used to identify high risk patients for early intensive management for renoprotection.