title: Variants in Vitamin D Binding Protein Gene Are Associated With Gestational Diabetes Mellitus.
abstract: To investigate whether single nucleotide polymorphisms (SNPs) within 4 representative genes (VDR, GC, CYP2R1, and CYP24A1) encoding the core proteins involved in vitamin D production, degradation, and ligand-dependent signaling pathway are associated with gestational diabetes mellitus (GDM) in a Chinese population. A total of 1494 pregnant Han Chinese women (692 women with GDM and 802 women with normal glucose served as controls) were recruited through a 2-step approach. Participants were further divided into 2 groups according to body mass index before gestation (pre-BMI) (25 kg/m2). Nine SNPs (rs3733359, rs2282679, and rs16847024 in GC, rs2060793 and rs10741657 in CYP2R1, rs2248359 and rs6013897 in CYP24A1, rs11574143 and rs739837 in VDR) were genotyped using TaqMan allelic discrimination assays. The relationships between genotypes/alleles of a single locus as well as haplotypes of each gene and GDM were analyzed. We did not observe a significant difference in genotype frequency of each SNP between cases and controls. However, in the obese subgroup (pre-BMI ≥ 25 kg/m2), the risk allele-A of rs3733359 showed an association with increased risk of GDM (OR = 1.739, 95% CI = 1.066-2.837, P = 0.027). The GG-haplotype frequency of rs3733359 and rs2282679 in GC was modestly lower in the GDM group (OR = 0.848, 95% CI = 0.719-0.999, P = 0.048). Rs2060793 and rs10741657 were associated with insulin area under the curve (P = 0.028, P = 0.042, respectively), while rs739837 and rs6013897 demonstrated a correlation with fasting glucose (P = 0.019, P = 0.049, respectively). Additionally, rs2248359 displayed an association with leukocyte counts (B = 0.063 P = 0.033) and rs16847024 was related to high-sensitivity C-reactive protein levels (B = 0.086, P = 0.005). Our results indicate an association between GC variants and GDM, as well as a relation between a subset of loci in CYP2R1, CYP24A1, and VDR and clinical parameters related to GDM. Our findings may provide information for identifying biomarkers for early risk prediction of GDM and the pathways involved in disease progression.
authors.affiliation: From the Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (YW, OW, WL, FP, MN); Key Laboratory of Endocrinology, Ministry of Health, Beijing, China (YW, OW, WL, FP, MN); People's Hospital of Longkou City, Shan Dong, China (YW); Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing China (LM); and Department of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China (LC).
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Liangkun
authors.initials: L
authors.lastname: Ma
authors.forename: Fan
authors.initials: F
authors.lastname: Ping
authors.forename: Limeng
authors.initials: L
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Nie
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002681:China / Q000453:epidemiology; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D016640:Diabetes, Gestational / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D018167:Receptors, Calcitriol / Q000235:genetics; D014809:Vitamin D-Binding Protein / Q000235:genetics*; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014809:Vitamin D-Binding Protein; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase