Correlation Of CDKAL1 Gene With Function Of Insulin Secretion And Glucose-related Traits

Objective:To investigate the association between the body mass index (BMI)-associated locus CDKAL1 with insulin secretion, insulin resistance, and glucose-related traits in Chinese Han population, further clarify the underlying mechanism associated with the gene that accounts for metabolic diseases. The aim of this study was to lay the foundation for early intervention and the development of genotype-based personalized strategies for diabetes treatment.Subjects and Methods:Samples were obtained from 2,313 participants (age range:18-81 years) of a community-based health examination survey in XuZhou, Jiangsu Province of China. All the participants underwent physical examination (height, weight, blood pressure), and biochemical tests [fasting blood glucose (FBG), fasting insulin,2-h plasma glucose, glycosylated hemoglobin (HbAlc), serum uric acid (SUA), cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)]. Insulin resistance and insulin secretion were assessed by homeostasis model assessment-insulin resistance index (HOMA-IR) and homeostasis model assessment of B-cell function index (HOMA-B). TaqMan probe technology was used to detect the alleles and genotypes of rs 10946398 genotype. SAS9.1.3 software was applied for data management and statistical analysis.Results:1. No significant baseline differences were observed with respect to age, blood pressure, TC, TG, HDL-C, LDL-C, SUA, insulin and HOMA-IR between genotypes, but the C allele of rs10946398 was associated with a higher FBG and lower HOMA-B.2. After adjusting for sex, age and BMI, the CDKAL1 rs10946398 C allele showed a significant association with decreased insulin secretion (Beta=-0.05, P< 0.0005), but not with insulin resistance (Beta= 0.02, P= 0.08). Further adjustments for other confounding factors did not qualitatively change the associations.3. After adjusting for sex, age and BMI, the CDKAL1 rs10946398 C allele was significantly associated with glucose-related traits (FBG, fasting insulin,2-h glucose, and HbAlc).4. The odds ratio of the risk of insulin resistance for genotypes was 1.21 (1.04-1.41) and that of decreased insulin secretion for genotypes was 1.29 (1.07-1.56) after adjusting for age, sex, and BMI. Further adjustment for more confounding factors still showed the statistical significance for HOMA-B (P<0.05) but not for HOMA-IR (P=0.13).Conclusions:1. rs10946398 of CDKAL1 was associated with HOMA-B, independent of other metabolic risk factors.2. Compared with the A allele, the C allele of rsl0946398 was associated with higher levels of FBG,2-h plasma glucose, HbAlc, independent of other metabolic risk factors.3. The C allele of rs10946398 was associated with markers of impaired insulin secretion, but not with insulin resistance. Further adjustment for more confounding factors still showed statistical significance.