Placental genetic variations in vitamin D metabolism and birthweight.
Vitamin D has pleiotropic functions that regulate fetal growth and development. We investigated associations of common placental genetic variations in vitamin D metabolism with birthweight.



The study was conducted among participants (506 maternal-infant pairs) of a pregnancy cohort study. Data were collected using interviewer-administered questionnaires and post-delivery medical record abstraction. DNA, extracted from placental samples collected at delivery, was genotyped for eight single nucleotide polymorphisms (SNPs) in five vitamin D metabolism genes (CUBN, LRP2, VDR, GC, and CYP2R1). Linear and logistic regression models were used to evaluate associations of SNPs with birthweight and risk of low birthweight, respectively. Effect modification of associations by infant sex was examined using stratified analyses and interaction terms in regression models.



Mean (standard-deviation) birthweight among all, male, and female infants was 3482.1 (549.9), 3544.6 (579.0) and 3419.2 (512.5) grams, respectively. Each copy of the minor allele of rs2282679 (GC) was associated with a 68.6 g (95%CI:3.1134.7 g) increase in birthweight overall. Sex-specific associations were observed for SNP rs4667591 (LRP2) (p-value for interaction < 0.001). Each copy of the minor allele of rs4667591 was associated with a 124.7 g (95%CI:20.1229.0 g) increase in birthweight among female infants, and a suggested 81.6 g decrease in birthweight among male infants (95%CI:-183.7,20.5 g).



Our study identified overall and sex-specific associations between placental genetic variations in vitamin D metabolism and birthweight. If confirmed by larger replication studies, observed associations may provide insight into mechanistic underpinnings of the relationships between placental vitamin D metabolism and birth size.
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States. Electronic address: tworkale@uw.edu.
Tsegaselassie
T
Workalemahu
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States.
Sylvia E
SE
Badon
Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, United States.
Michal
M
Dishi-Galitzky
Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, United States.
Chunfang
C
Qiu
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Michelle A
MA
Williams
Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, United States.
Tanya
T
Sorensen
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States; Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, United States.
Daniel A
DA
Enquobahrie
D000328:Adult; D000483:Alleles; D001724:Birth Weight / Q000235:genetics*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D000072467:Cytochrome P450 Family 2 / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics; D008297:Male; D010920:Placenta / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D018167:Receptors, Calcitriol / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
C000597357:LRP2 protein, human; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D018167:Receptors, Calcitriol; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase
Birthweight; Genetic variation; Placenta; Vitamin D