Placental genetic variations in vitamin D metabolism and birthweight |
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| Affiliation: | 1. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States;2. Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, United States;3. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States;1. Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo 113-8602, Japan;2. Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan;3. Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan;1. Obstetrical Department, No.215 Hospital of Shanxi Nuclear Industry, Xianyang, Shaanxi, 712000, China;2. Obstetrical Department, Yan''an University Affiliated Hospital, Yan''an, Shaanxi, 716000, China;3. The 2nd Department of Obstetrical, Northwest Women and Children''s Hospital, Xian, Shaanxi, 710000, China;4. Obstetrical Department, Northwest Women and Children''s Hospital, Xian, Shaanxi, 710000, China;5. Gynaecology and Obstetrics, 4th (Xing Yuan) Hospital of Yulin, Yulin, Shaanxi, 719000, China;6. Gynaecology and Obstetrics, Xian NO.1 Hospital, Xian, Shaanxi, 710000, China;7. Obstetrical Department, Shaanxi Baoji Maternal and Child Health Hospital, Baoji 721000, China;8. Obstetrical Department, Yan''an People''s Hospital, Yanan, Shaanxi, 716000, China;1. Embryo Implantation Laboratory, Hudson Institute, Clayton, VIC, Australia;2. Department of Molecular and Translational Medicine, Monash University, Clayton, VIC, Australia;3. Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia;1. Institute of Arthritis Research, 2220 East 25th St, Idaho Falls, ID 83404, USA;2. Idaho State University, Department of Biology, 921 South 8th Avenue, Pocatello, ID 83201, USA |
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| Abstract: | IntroductionVitamin D has pleiotropic functions that regulate fetal growth and development. We investigated associations of common placental genetic variations in vitamin D metabolism with birthweight.MethodsThe 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.ResultsMean (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).DiscussionOur 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. |
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| Keywords: | Birthweight Vitamin D Placenta Genetic variation |
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