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Full length article| Volume 220, P61-68, January 2018

Vitamin D metabolic loci and vitamin D status in Black and White pregnant women

  • Katharyn M. Baca
    Affiliations
    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA
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  • Manika Govil
    Affiliations
    Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA
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  • Joseph M. Zmuda
    Affiliations
    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA

    Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 15261, USA
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  • Hyagriv N. Simhan
    Affiliations
    Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, 300 Halket Street, Pittsburgh, PA, 15213, USA

    Magee-Womens Research Institute, Pittsburgh, PA, 15213, USA
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  • Mary L. Marazita
    Affiliations
    Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 15261, USA

    Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA
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  • Lisa M. Bodnar
    Correspondence
    Corresponding author at: University of Pittsburgh, Graduate School of Public Health, 130 DeSoto St, Pittsburgh, PA, 15261, USA.
    Affiliations
    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA

    Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, 300 Halket Street, Pittsburgh, PA, 15213, USA

    Magee-Womens Research Institute, Pittsburgh, PA, 15213, USA
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Published:November 16, 2017DOI:https://doi.org/10.1016/j.ejogrb.2017.11.013

      Abstract

      Background

      Several candidate genes and genome wide association studies have reported significant associations between vitamin D metabolism genes and 25-hydroxyvitamin D. Few studies have examined these relationships in pregnancy.

      Objective

      We evaluated the relationship between maternal allelic variants in three vitamin D metabolism genes and 25-hydroxyvitamin D (25(OH)D) concentration in pregnancy.

      Study design

      In two case-control studies, samples were drawn from women who delivered at Magee Womens Hospital in Pittsburgh, PA from 1999 to 2010 and twelve recruiting sites across the United States from 1959 to 65. For 882 Black and 1796 White pregnant women from these studies, 25(OH)D concentration was measured and single nucleotide polymorphisms (SNPs) were genotyped 50 kilobases up- and down-stream in three genes (VDR, GC, and CYP27B1). Using multivariable linear regression, we estimated the associations between allelic variation of each locus and log-transformed 25(OH)D concentration separately by race and study group. Meta-analysis was used to estimate the association across the four groups for each SNP.

      Results

      Minor alleles of several variants in VDR, GC, and CYP27B1 were associated with differences in log-transformed 25(OH)D concentration compared to the corresponding major alleles [beta, 95% confidence intervals (CI)]. The meta-analysis confirmed the associations for differences in log-transformed 25(OH)D by allelic loci for one intron VDR variant [rs2853559 0.08 (0.02, 0.13), p < 0.01] and a variant in the GC flanking region [rs13150174: 0.04 (0.02, 0.07), p < 0.01], and a GC missense mutation [rs7041 0.05 (0.01, 0.09), p < 0.01]. The meta-analysis also revealed possible associations for SNPs in linkage disequilibrium with variants in the VDR 3-prime untranslated region, another GC missense variant (rs4588), and a variant of the 3-prime untranslated region of CYP27B1.

      Conclusion

      We observed associations between VDR, GC, and CYP27B1 variants and maternal 25-hydroxyvitamin D concentration. Our results provide additional support for a possible role of genetic variation in vitamin D metabolism genes on vitamin D status during pregnancy.

      Abbreviations:

      25(OH)D (25-hydroxyvitamin D), CYP27B1 (1 alpha-hydroxylase), GC (vitamin D binding protein), VDR (vitamin D receptor), chr. (chromosome), SNP (single nucleotide polymorphisms), 25(OH)D (25-hydroxyvitamin D), BMI (body-mass index), ICD-9 (International Classification of Diseases), OR (odds ratio), CI (confidence interval), ASW (Americans of African Ancestry in Southwest USA), CEU (Utah residents with Northern and Western European ancestry)

      Keywords

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