title: Genetic variants in vitamin D signaling pathways and risk of gestational diabetes mellitus.
abstract: Vitamin D (VD) deficiency during pregnancy has been repeatedly linked to an increased gestational diabetes mellitus (GDM) risk. We sought to determine the influences of genetic variants in vitamin D signaling pathways on the risk of GDM. In this study, we genotyped 15 single nucleotide polymorphisms (SNPs) within 8 representative genes (CYP27A1, CYP27B1, CYP24A1, VDR, RXRA, RXRB, RXRG and GC) of the vitamin D signaling pathways in a case-control study with 964 GDM cases and 1,021 controls using the Sequenom MassARRAY iPLEX platform. Logistic regression analyses in additive model showed that GC rs16847024 C>T, RXRG rs17429130 G>C and RXRA rs4917356 T>C were significantly associated with the increased risk of GDM (adjusted OR = 1.31, 95% CI = 1.10-1.58 for rs16847024; adjusted OR = 1.28, 95% CI = 1.04-1.57 for rs17429130; adjusted OR = 1.28, 95% CI = 1.06-1.54 for rs4917356). And GDM risk significantly increased with the increasing number of variant alleles of the three SNPs in a dose-dependent manner (P for trend < 0.001). Moreover, the combined effect of the three SNPs on GDM occurrence was more prominent in older women (age > 30). Further interactive analyses also detected a significantly multiplicative interaction between the combined variant alleles and age on GDM risk (P = 0.035). Together, these findings indicate that GC rs16847024, RXRG rs17429130 and RXRA rs4917356 were candidate susceptibility markers for GDM in Chinese females. Further validation studies with different ethnic background and biological function analyses were needed.
authors.affiliation: Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.|Department of MICU, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.|State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Aiwu
authors.initials: A
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.|Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.|Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wen
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Guangquan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.|Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of MICU, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of MICU, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of MICU, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Yaoqiu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.|Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.|Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Xirong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D016640:Diabetes, Gestational / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047490:Retinoid X Receptor alpha / Q000235:genetics; D047491:Retinoid X Receptor gamma / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D014807:Vitamin D / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000208:ethnology / Q000235:genetics; D014809:Vitamin D-Binding Protein / Q000235:genetics
chemical_list: D047490:Retinoid X Receptor alpha; D047491:Retinoid X Receptor gamma; D014809:Vitamin D-Binding Protein; D014807:Vitamin D
keywords: Pathology Section; gestational diabetes mellitus; pathway; polymorphism; vitamin D