Research Papers: Pathology:
Genetic variants in vitamin D signaling pathways and risk of gestational diabetes mellitus
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Aiwu Shi1,2,3,*, Juan Wen3,4,5,*, Guangquan Liu4,*, Heng Liu4, Ziyi Fu3,4, Jing Zhou2, Yao Zhu2, Yaoqiu Liu2, Xirong Guo3,4,5 and Jianguo Xu1
1 Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
2 Department of MICU, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China
3 State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China
4 Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China
5 Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China
* These authors have contributed equally to this work
Jianguo Xu, email:
Keywords: vitamin D; pathway; polymorphism; gestational diabetes mellitus; Pathology Section
Received: July 13, 2016 Accepted: September 07, 2016 Published: September 12, 2016
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.
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