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
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Obstetrics and Gynecology and Reproductive BiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Vitamin D status: United States, 2001–2006.NCHS Data Brief. 2011; 59: 1-8
- High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates.J Nutr. 2007; 137: 447-452
- Vitamin D deficiency and insufficiency is common during pregnancy.Am J Perinatol. 2011; 28: 7-12
- Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline.J Clin Endocrinol Metabo. 2011; 96: 1911-1930
- Prevalence and correlates of vitamin D deficiency in US adults.Nutr Res (New York, NY). 2011; 31: 48-54
- Vitamin D deficiency in minority populations.Public Health Nutr. 2015; 18: 379-391
- Rickets.Lancet. 2014; 383: 1665-1676
- Vitamin D and pregnancy outcomes.Curr Opin Obstetrics Gynecol. 2014; 26: 438-447
- Vitamin D and pre-eclampsia: original data, systematic review and meta-analysis.Ann Nutrit Metab. 2013; 63: 331-340
- Maternal vitamin D status and adverse pregnancy outcomes: a systematic review and meta-analysis.J Mater-Fetal Neonatal Med. 2013; 26: 889-899
- Efficacy of high-dose vitamin D in pediatric asthma: a systematic review and meta-analysis.J Asthma. 2015; 52: 382-390
- The role of vitamin D deficiency in the incidence, progression, and complications of type 1 diabetes mellitus.Int J Endocrinol. 2013; 2013: 148673
- Common genetic determinants of vitamin D insufficiency: a genome-wide association study.Lancet. 2010; 376: 180-188
- Genome-wide association study of circulating vitamin D levels.Hum Mol Genet. 2010;
- Common variation in vitamin D pathway genes predicts circulating 25-hydroxyvitamin D levels among African Americans.PLoS One. 2011; 6: e28623
- Vitamin D in pregnancy and lactation in humans.Annu Rev Nutr. 2011; 31: 89-115
- Vitamin D and placental-decidual function.J Soc Gynecol Invest. 2004; 11: 263-271
- Vitamin D effects on pregnancy and the placenta.Placenta. 2010; 31: 1027-1034
- Early-pregnancy vitamin D deficiency and risk of preterm birth subtypes.Obstet Gynecol. 2015; 125: 439-447
- Maternal vitamin D status and the risk of mild and severe preeclampsia.Epidemiology. 2014; 25: 207-214
- The measurement of vitamin D: analytical aspects.Ann Clin Biochem. 2004; 41: 272-281
- Racial and seasonal differences in 25-hydroxyvitamin D detected in maternal sera frozen for over 40 years.Br J Nutr. 2009; 101: 278-284
- Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy.J Clin Endocrinol Metab. 2005; 90: 3215-3224
- The international HapMap project.Nature. 2003; 426: 789-796
- Inference of population structure using multilocus genotype data.Genetics. 2000; 155: 945-959
- Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies.Genetics. 2003; 164: 1567-1587
- Inference of population structure using multilocus genotype data: dominant markers and null alleles.Mol Ecol Notes. 2007; 7: 574-578
- Inferring weak population structure with the assistance of sample group information.Mol Ecol Res. 2009; 9: 1322-1332
- Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America.Hum Mutat. 2009; 30: 69-78
- The immunological functions of the vitamin D endocrine system.Cell Mol Biol (Noisy-le-Grand, France). 2003; 49: 277-300
- The Collaborative Perinatal Study of the National Institute of Neurological Diseases and Stroke: The Women and Their Pregnancies.WB Saunders, Philadelphia, PA1972
- Detecting the number of clusters of individuals using the software STRUCTURE: a simulation study.Mol Ecol. 2005; 14: 2611-2620
- Data quality control in genetic case-control association studies.Nat Protocols. 2010; 5: 1564-1573
- PLINK: a toolset for whole-genome association and population-based linkage analysis.Am J Hum Genet. 2007; : 81
- Establishing an adjusted p-value threshold to control the family-wide type 1 error in genome wide association studies.BMC Genomics. 2008; 9 (516-516)
- HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants.Nucleic Acids Res. 2011; (40(Database issue) D930-4)
- Splice variants of the CYP27b1 gene and the regulation of 1,25-dihydroxyvitamin D3 production.Endocrinology. 2007; 148: 3410-3418
- Maternal 25-hydroxyvitamin D concentration and offspring birth size: effect modification by infant VDR genotype.Eur J Clin Nutr. 2009; 63: 802-804
- Promoter and 3′-untranslated-region haplotypes in the vitamin D receptor gene predispose to osteoporotic fracture: the rotterdam study.Am J Hum Genet. 2005; 77: 807-823
- Vitamin D–binding protein and vitamin D status of black americans and white americans.New Engl J Med. 2013; 369: 1991-2000
- Genome-wide association study of circulating vitamin D levels.Hum Mol Genet. 2010; 19: 2739-2745
- Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women.Am J Clin Nutr. 2009; 89: 634-640
- Genome-wide association study of vitamin D concentrations in Hispanic Americans: the IRAS family study.J Steroid Biochem Mol Biol. 2010; 122: 186-192
- Common genetic variants of the vitamin D binding protein (DBP) predict differences in response of serum 25-hydroxyvitamin D [25(OH)D] to vitamin D supplementation.Clin Biochem. 2009; 42: 1174-1177
- Vitamin D binding protein genotype and osteoporosis.Calcif Tissue Int. 2009; 85: 85-93
- Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromsø Study.PLoS One. 2012; 7
- Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis.Am J Clin Nutr. 2008; 88: 441-447
- CYP24A1 and CYP27B1 polymorphisms modulate vitamin D metabolism in colon cancer cells.Cancer Res. 2013; 73: 2563-2573
- Wellcome: genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.Nature. 2007; 447: 661-678
Article info
Publication history
Published online: November 16, 2017
Accepted:
November 13,
2017
Received in revised form:
October 19,
2017
Received:
May 31,
2017
Identification
Copyright
© 2017 Published by Elsevier Ireland Ltd.
