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Variation in the Maternal Corticotrophin Releasing Hormone-Binding Protein (CRH-BP) Gene and Birth Weight in Blacks, Hispanics and Whites

Wadhwa, PD and Simhan, HN and Entringer, S and Buss, C and Smith, R and Hobel, CJ and Farhana, N and Shimmin, L and Hixson, JE and Sing, CF (2012) Variation in the Maternal Corticotrophin Releasing Hormone-Binding Protein (CRH-BP) Gene and Birth Weight in Blacks, Hispanics and Whites. PLoS ONE, 7 (9).

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Abstract

Background: Given the unique role of the corticotrophin-releasing hormone (CRH) system in human fetal development, the aim of our study was to estimate the association of birth weight with DNA sequence variation in three maternal genes involved in regulating CRH production, bioavailability and action: CRH, CRH-Binding Protein (CRH-BP), and CRH type 1 receptor (CRH-R1), respectively, in three racial groups (African-Americans, Hispanics, and non-Hispanic Whites). Methods: Our study was carried out on a population-based sample of 575 mother-child dyads. We resequenced the three genes in mouse-human hybrid somatic cell lines and selected SNPs for genotyping. Results: A significant association was observed in each race between birth weight and maternal CRH-BP SNP genotypes. Estimates of linkage disequilibrium and haplotypes established three common haplotypes marked by the rs1053989 SNP in all three races. This SNP predicted significant birth weight variation after adjustment for gestational age, maternal BMI, parity, and smoking. African American and Hispanic mothers carrying the A allele had infants whose birth weight was on average 254 and 302 grams, respectively, less than infants having C/C mothers. Non-Hispanic White mothers homozygous for the A allele had infants who were on average 148 grams less than those infants having A/C and C/C mothers. Conclusions: The magnitudes of the estimates of the birth weight effects are comparable to the combined effects of multiple SNPs reported in a recent meta-analysis of 6 GWAS studies and is quantitatively larger than that associated with maternal cigarette smoking. This effect was persistent across subpopulations that vary with respect to ancestry and environment. © 2012 Wadhwa et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wadhwa, PD
Simhan, HNhns6@pitt.eduHNS6
Entringer, S
Buss, C
Smith, R
Hobel, CJ
Farhana, N
Shimmin, L
Hixson, JE
Sing, CF
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorWang, Yan-LingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 11 September 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 9
DOI or Unique Handle: 10.1371/journal.pone.0043931
Schools and Programs: School of Medicine > Obstetrics, Gynecology, and Reproductive Sciences
Refereed: Yes
Other ID: NLM PMC3439482
PubMed Central ID: PMC3439482
PubMed ID: 22984453
Date Deposited: 19 Oct 2012 21:23
Last Modified: 04 Feb 2019 15:58
URI: http://d-scholarship.pitt.edu/id/eprint/15902

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