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

Abstract

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.

Keywords: E23K; gender; polymorphism; potassium voltage-gated channel subfamily J member 11 (KCNJ11); prediabetes; 内向整流钾通道亚家族成员11(KCNJ11); 多态性; 性别; 糖尿病前期.