The CDKAL 1 gene is associated with impaired insulin secretion and glucose‐related traits: the Cardiometabolic Risk in Chinese (CRC) study

Summary Objective Insulin secretion and insulin resistance, which affect metabolic homoeostasis, each have a significant genetic component. Cyclin‐ dependent kinase 5 ( CDK 5) regulatory subunit‐associated protein 1‐like 1 ( CDKAL 1) rs10946398, a novel body mass index ( BMI )‐associated locus specifically in the Asian population, may impair insulin secretion and may be associated with insulin resistance and type 2 diabetes . Our objective was to investigate the impact of the rs10946398 polymorphism of CDKAL 1 on insulin secretion, insulin resistance and glucose‐related traits in the Chinese population. Subjects and Methods The study samples were based on a community‐based health examination survey conducted in central China. Indices of insulin resistance and insulin secretion were derived from fasting glucose measurements and oral glucose tolerance tests ( OGTT s). Using multivariate linear regression models, the relationships between the rs10946398 polymorphism of CDKAL 1 and insulin secretion, insulin resistance and quantitative glucose‐related traits were investigated in 2313 participants. Results The CDKAL 1 rs10946398 C allele showed a significant association with decreased insulin secretion (β = −0·05, P  <   0·0005), but not with insulin resistance (β = 0·02, P  =   0·08). We also found that the CDKAL 1 rs10946398 C allele was significantly associated with glucose‐related traits (fasting glucose, fasting insulin, 2‐h glucose and HbA1c). There was no significant relationship between rs10946398 and other metabolic traits. Conclusions rs10946398 of CDKAL 1 was associated with markers of impaired insulin secretion. It is reasonable to infer that the relationship between CDKAL 1 and metabolic diseases is mediated by its effect on glucose‐related traits.