Prediabetes is associated with genetic variations in the gene encoding the Kir6.2 subunit of the pancreatic ATP‐sensitive potassium channel (KCNJ11): A case‐control study in a Han Chinese youth population

• Published in: Journal of diabetes Vol. 10; no. 2; pp. 121 - 129
• Main Authors: Xu, Min, Hu, Honglin, Deng, Datong, Chen, Mingwei, Xu, Zhenshan, Wang, Youmin
• Format: Journal Article
• Language: English
• Published: Melbourne Wiley Publishing Asia Pty Ltd 01.02.2018; John Wiley & Sons, Inc
• Subjects: Adolescent; Asian Continental Ancestry Group - genetics; Biomarkers - analysis; Blood Glucose - analysis; Case-Control Studies; China - epidemiology; Cholesterol; E23K; Female; Follow-Up Studies; gender; Genetic Predisposition to Disease; Genotype; Glycated Hemoglobin A - analysis; Humans; Insulin; Male; polymorphism; Polymorphism, Genetic; Potassium; Potassium Channels, Inwardly Rectifying - genetics; potassium voltage‐gated channel subfamily J member 11 (KCNJ11); prediabetes; Prediabetic State - epidemiology; Prediabetic State - genetics; Prognosis; 内向整流钾通道亚家族成员11(KCNJ11); 多态性; 性别; 糖尿病前期; 糖尿病前期; gender; E23K; prediabetes; polymorphism; 多态性; potassium voltage-gated channel subfamily J member 11 (KCNJ11); 内向整流钾通道亚家族成员11(KCNJ11); 性别
• ISSN: 1753-0393; 1753-0407; 1753-0407
• DOI: 10.1111/1753-0407.12565

Background The E23K variant of the potassium voltage‐gated channel subfamily J member 11 (KCNJ11) gene has been reported to be associated with type 2 diabetes (T2D) in many populations. However, little is known about the role of E23K in the development of prediabetes in Chinese youth. Methods To investigate the role of E23K in the development of prediabetes, 279 subjects with prediabetes and 240 normal controls (mean [± SD] age 18.1 ± 3.2 and 17.8 ± 4.3 years, respectively) were recruited to the study. Height, weight, and hip and waist circumferences were measured by trained physicians. Genotyping of KCNJ11 polymorphisms and clinical laboratory tests to determine cholesterol, triglyceride (TG), blood glucose, and insulin levels were performed. Results The carrier rate of K23 allele‐containing genotypes was higher for prediabetic than control subjects (P = 0.005). Logistic regression analyses revealed that higher body mass index percentiles (P = 0.013), lower insulin levels at 30 min during an oral glucose tolerance test (P = 0.001), a higher ratio of total cholesterol: high‐density lipoprotein cholesterol (P = 0.001), and a K allele‐containing genotype (P = 0.019) are independent risk factors for prediabetes in Chinese Han youth. Furthermore, K23 allele‐containing genotypes were associated with impaired indices of insulin secretion and β‐cell function in female youth with prediabetes. These effects were not seen in male youth with prediabetes. Conclusions The results confirm that the common E23K polymorphism of KCNJ11 carries a higher susceptibility to the development of prediabetes in the Chinese Han population. The results suggest that E23K may have a greater effect on the development of T2D in female Chinese youth. 摘要 背景 已有报道内向整流钾通道亚家族成员11(potassium voltage‐gated channel subfamily J member 11,  KCNJ11)E23K 基因多态性在多个人群中与2型糖尿病相关。但对于E23K对中国青年人群发展为糖尿病前期的作用仍知之甚少。 方法 调查E23K对发展为糖尿病前期的作用。研究纳入了279名糖尿病前期受试者以及240名正常对照者(平均[±SD]年龄分别为18.1 ± 3.2和17.8 ± 4.3岁)。由医务人员测量其身高、体重、腰臀比。还进行了KCNJ11多态性的基因分型并检测了胆固醇、甘油三酯、血糖和胰岛素水平等临床实验室指标。 结果 糖尿病前期受试者的K23等位基因携带率显著高于对照组(P = 0.005),  logistic回归分析显示体重指数处于较高百分位数(P = 0.013)、口服糖耐量试验的30分钟胰岛素水平较低(P = 0.001)、总胆固醇与高密度脂蛋白比例较高(P = 0.001)以及携带K等位基因(P = 0.019)为中国汉族青年人群发生糖尿病前期的独立危险因子。此外,  在糖尿病前期的中国青年女性中,  携带K23等位基因与胰岛素分泌和β‐细胞功能受损相关,  在男性中没有见到这种相关性。 结论 本研究的结果证实了在中国青年人群中,  携带KCNJ11常见的E23K基因多态性与发展为糖尿病前期高度相关。该结果还提示了EK23对于中国青年女性发展为糖尿病前期具有重要影响。 Highlight Our results suggest that common polymorphism of E23K of the KCNJ11 carries higher susceptibility to the development of prediabetes in Chinese Han population. It is also found that E23K variant of the KCNJ11 may have a greater impact on the development of type 2 diabetes in female youth in China.