Jun Liang1,2, Ying Pei3, Xuekui Liu1,2, Qinqin Qiu4, Yuting Sun4, Yan Zhu4, Manqing Yang1,2, Lu Qi5. 1. Department of Endocrinology, Xuzhou Central Hospital, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu, China. 2. Xuzhou Institute of Medical Sciences, Xuzhou Institute of Diabetes, Xuzhou, Jiangsu, China. 3. School of Medicine, Southeast University, Nanjing, China. 4. Xuzhou Medical College, Xuzhou, Jiangsu, China. 5. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
Abstract
OBJECTIVE: Insulin secretion and insulin resistance, which affect metabolic homoeostasis, each have a significant genetic component. Cyclin- dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1) 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 CDKAL1 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 (OGTTs). Using multivariate linear regression models, the relationships between the rs10946398 polymorphism of CDKAL1 and insulin secretion, insulin resistance and quantitative glucose-related traits were investigated in 2313 participants. RESULTS: The CDKAL1 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 CDKAL1 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 CDKAL1 was associated with markers of impaired insulin secretion. It is reasonable to infer that the relationship between CDKAL1 and metabolic diseases is mediated by its effect on glucose-related traits.
OBJECTIVE:Insulin secretion and insulin resistance, which affect metabolic homoeostasis, each have a significant genetic component. Cyclin- dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1) 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 CDKAL1 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 (OGTTs). Using multivariate linear regression models, the relationships between the rs10946398 polymorphism of CDKAL1 and insulin secretion, insulin resistance and quantitative glucose-related traits were investigated in 2313 participants. RESULTS: The CDKAL1rs10946398 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 CDKAL1rs10946398 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 CDKAL1 was associated with markers of impaired insulin secretion. It is reasonable to infer that the relationship between CDKAL1 and metabolic diseases is mediated by its effect on glucose-related traits.
Authors: Yulia A Nasykhova; Ziravard N Tonyan; Anastasiia A Mikhailova; Maria M Danilova; Andrey S Glotov Journal: Int J Mol Sci Date: 2020-09-18 Impact factor: 5.923