title: Variation in the maternal corticotrophin releasing hormone-binding protein (CRH-BP) gene and birth weight in Blacks, Hispanics and Whites.
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.
authors.affiliation: Departments of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, United States of America. pwadhwa@uci.edu
authors.forename: Pathik D
authors.initials: PD
authors.lastname: Wadhwa
authors.forename: Hyagriv N
authors.initials: HN
authors.lastname: Simhan
authors.forename: Sonja
authors.initials: S
authors.lastname: Entringer
authors.forename: Claudia
authors.initials: C
authors.lastname: Buss
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
authors.forename: Calvin J
authors.initials: CJ
authors.lastname: Hobel
authors.forename: Naveed
authors.initials: N
authors.lastname: Farhana
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shimmin
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.forename: Charles F
authors.initials: CF
authors.lastname: Sing
mesh_terms: D000328:Adult; D000818:Animals; D001724:Birth Weight / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007223:Infant; D051379:Mice; D009035:Mothers; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: D002352:Carrier Proteins; C067133:corticotropin releasing factor-binding protein