Wang Ke, Shi Mai, Yang Aimin, Fan Baoqi, Tam Claudia H T, Lau Eric, Luk Andrea O Y, Kong Alice P S, Ma Ronald C W, Chan Juliana C N, Chow Elaine
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
Diabetes Res Clin Pract. 2022 Nov;193:110118. doi: 10.1016/j.diabres.2022.110118. Epub 2022 Oct 13.
Glucokinase (GCK) and glucokinase regulatory protein (GKRP) regulate glucose and lipid metabolism. We investigated the associations of GCKR and GCK polymorphisms with kidney outcomes.
Analyses 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.
6072 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.
In 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.
葡萄糖激酶（GCK）和葡萄糖激酶调节蛋白（GKRP）调节葡萄糖和脂质代谢。我们研究了GCKR和GCK基因多态性与肾脏结局的关联。
对1995年至2017年纳入香港糖尿病登记册的前瞻性队列进行分析。通过Cox回归或逻辑回归分析GCKR rs1260326和GCK rs1799884基因多态性与新发终末期肾病（ESKD）、蛋白尿和估算肾小球滤过率（eGFR）快速下降的关联，并进行校正。
纳入6072例患者（基线平均年龄57.4岁；糖尿病病程中位数6.0年；54.5%为女性），中位随访15.5年。与各自的CC基因型相比，GCKR rs1260326 [CT的风险比（HR）（95%置信区间）为1.23（1.05 - 1.44）；TT为1.23（1.02 - 1.48）]和GCK rs1799884 T等位基因[TT为1.73（1.24 - 2.40）]与ESKD风险增加独立相关。GCKR rs1260326 T等位基因也与蛋白尿[CT的比值比（OR）为1.18（1.05 - 1.33）；TT为1.34（1.16 - 1.55）]和eGFR快速下降相关。
在中国2型糖尿病患者中，GCKR rs1260326和GCK rs1799884的T等位基因携带者发生ESKD的风险较高。这些遗传标志物可用于识别高危患者，以便进行早期强化肾脏保护管理。
