Tsegaselassie Workalemahu1, Sylvia E Badon2, Michal Dishi-Galitzky3, Chunfang Qiu3, Michelle A Williams4, Tanya Sorensen3, Daniel A Enquobahrie5. 1. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States. Electronic address: tworkale@uw.edu. 2. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States. 3. Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, United States. 4. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States. 5. 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.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.
INTRODUCTION: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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.
Authors: Daniel A Enquobahrie; Margaret Meller; Kenneth Rice; Bruce M Psaty; David S Siscovick; Michelle A Williams Journal: Am J Obstet Gynecol Date: 2008-06-04 Impact factor: 8.661
Authors: Galina Lurie; Lynne R Wilkens; Pamela J Thompson; Michael E Carney; Rachel T Palmieri; Paul D P Pharoah; Honglin Song; Estrid Hogdall; Susanne Kruger Kjaer; Richard A DiCioccio; Valerie McGuire; Alice S Whittemore; Simon A Gayther; Aleksandra Gentry-Maharaj; Usha Menon; Susan J Ramus; Marc T Goodman Journal: Int J Cancer Date: 2011-02-15 Impact factor: 7.396
Authors: Lisa M Bodnar; Janet M Catov; Joseph M Zmuda; Margaret E Cooper; Meredith S Parrott; James M Roberts; Mary L Marazita; Hyagriv N Simhan Journal: J Nutr Date: 2010-03-03 Impact factor: 4.798
Authors: Zengjing Liu; Adam A Szpiro; Tsegaselassie Workalemahu; Michael T Young; Joel D Kaufman; Daniel A Enquobahrie Journal: Environ Res Date: 2021-09-22 Impact factor: 6.498
Authors: Leslea J Hlusko; Joshua P Carlson; George Chaplin; Scott A Elias; John F Hoffecker; Michaela Huffman; Nina G Jablonski; Tesla A Monson; Dennis H O'Rourke; Marin A Pilloud; G Richard Scott Journal: Proc Natl Acad Sci U S A Date: 2018-04-23 Impact factor: 11.205
Authors: Martina Barchitta; Andrea Maugeri; Maria Clara La Rosa; Roberta Magnano San Lio; Giuliana Favara; Marco Panella; Antonio Cianci; Antonella Agodi Journal: Nutrients Date: 2018-08-27 Impact factor: 5.717
Authors: Hubert Wolski; Grażyna Kurzawińska; Marcin Ożarowski; Aleksandra E Mrozikiewicz; Krzysztof Drews; Tomasz M Karpiński; Anna Bogacz; Agnieszka Seremak-Mrozikiewicz Journal: Sci Rep Date: 2021-02-25 Impact factor: 4.379
Authors: Michał Ciebiera; Cezary Wojtyła; Krzysztof Łukaszuk; Magdalena Zgliczyńska; Kornelia Zaręba; Wojciech Rawski; Grzegorz Jakiel Journal: Arch Med Sci Date: 2019-01-30 Impact factor: 3.318