title: Association of variants in CDKN2A/2B and CDKAL1 genes with gestational insulin sensitivity and disposition in pregnant Han Chinese women.
abstract: OBJECTIVE
  Variants in cell cycle regulation genes, CDKAL1 and CDKN2A/2B, have been suggested to be associated with type 2 diabetes, and also play a role in insulin procession in non-diabetic European individuals. Rs7754580 in CDKAL1 and rs7020996 in CDKN2A/2B were found to be associated with gestational diabetes in Chinese individuals. In order to understand the metabolism mechanism of greatly upregulated maternal insulin signaling during pregnancy and the pathogenesis of gestational diabetes, we investigated the impact of rs7754580 and rs7020996 on gestational insulin regulation and procession.
  
  
  METHODS
  We recruited 1,146 unrelated, non-diabetic, pregnant Han Chinese women (age 28.5 ± 4.1 years, body mass index 21.4 ± 2.6 kg/m(2)), and gave them oral glucose tolerance tests. The indices of insulin sensitivity, insulin disposition, insulin release and proinsulin to insulin conversion were calculated. Rs7754580 in the CDKAL1 gene and rs7020996 in the CDKN2A/2B gene were genotyped. Under an additive model, we analyzed the associations between the variants and gestational insulin indices using logistic regression.
  
  
  RESULTS
  By adjusting for maternal age, body mass index and the related interactions, CDKAL1 rs7754580 risk allele C was detected to be associated with increased insulin sensitivity (P = 0.011), decreased insulin disposition (P = 0.0002) and 2-h proinsulin conversion (P = 0.017). CDKN2A/2B rs7020996 risk allele T was found to be related to decreased insulin sensitivity (P = 0.002) and increased insulin disposition (P = 0.0001).
  
  
  CONCLUSIONS
  The study showed that cell cycle regulating genes might have a distinctive effect on gestational insulin sensitivity, β-cell function and proinsulin conversion in pregnant Han Chinese women.
authors.affiliation: Department of Obstetrics and Gynecology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Mei
authors.affiliation: Diabetes Center & Institute of Transplantation, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, China.
authors.forename: Shunyao
authors.initials: S
authors.lastname: Liao
authors.affiliation: Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University Chengdu, China.
authors.forename: Yunqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Science, Hunan Normal University Changsha, Hunan, China.
authors.forename: Yuande
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Diabetes Center & Institute of Transplantation, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, China.
authors.forename: Hailian
authors.initials: H
authors.lastname: Wang
authors.affiliation: Diabetes Center & Institute of Transplantation, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Diabetes Center & Institute of Transplantation, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, China.
authors.forename: Xianjue
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Nuclear Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, China.
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Song
authors.affiliation: Diabetes Center & Institute of Transplantation, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Diabetes Center & Institute of Transplantation, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, China ; Human Islet Laboratory, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Deng
keywords: Genetic association; Gestational metabolisms; Insulin index