title: The CDKAL1 gene is associated with impaired insulin secretion and glucose-related traits: the Cardiometabolic Risk in Chinese (CRC) study.
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.
  
  
  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.
authors.affiliation: Department of Endocrinology, Xuzhou Central Hospital, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu, China.|Xuzhou Institute of Medical Sciences, Xuzhou Institute of Diabetes, Xuzhou, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.affiliation: School of Medicine, Southeast University, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Pei
authors.affiliation: Department of Endocrinology, Xuzhou Central Hospital, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu, China.|Xuzhou Institute of Medical Sciences, Xuzhou Institute of Diabetes, Xuzhou, Jiangsu, China.
authors.forename: Xuekui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Xuzhou Central Hospital, The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu, China.|Xuzhou Institute of Medical Sciences, Xuzhou Institute of Diabetes, Xuzhou, Jiangsu, China.
authors.forename: Manqing
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002681:China; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012359:tRNA Methyltransferases
chemical_list: D007328:Insulin; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human