Dataset Information

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.

SUBMITTER: Wadhwa PD

PROVIDER: S-EPMC3439482 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Variation in the maternal corticotrophin releasing hormone-binding protein (CRH-BP) gene and birth weight in Blacks, Hispanics and Whites.

Wadhwa Pathik D PD Simhan Hyagriv N HN Entringer Sonja S Buss Claudia C Smith Roger R Hobel Calvin J CJ Farhana Naveed N Shimmin Lawrence L Hixson James E JE Sing Charles F CF

PloS one 20120911 9

<h4>Background</h4>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).<h4>Methods</h4>Our study wa ...[more]

PMID: 22984453

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Project description:BackgroundHypertension is a significant risk factor for intracerebral hemorrhage (ICH). Although ethnic/racial disparities related to hypertension and ICH have been reported, these previous studies were limited by a lack of Hispanics and inadequate power to analyze by ICH location. In the current study, while overcoming these prior limitations, we investigated whether there was variation by ethnicity/race of treated and untreated hypertension as risk factors for ICH.MethodsThe ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage) is a prospective, multicenter, case-control study of ICH among whites, blacks, and Hispanics. Cases were enrolled from 42 recruitment sites. Controls matched to cases 1:1 by age (±5 years), sex, ethnicity/race, and metropolitan area were identified by random-digit dialing. Subjects were interviewed to determine history of hypertension and use of antihypertensive medications. Cases and controls within ethnic groups were compared by using conditional logistic regression. Multivariable conditional logistic regression models were computed for ICH as an overall group and separately for the location subcategories deep, lobar, and infratentorial (brainstem/cerebellar).ResultsNine hundred fifty-eight white, 880 black, and 766 Hispanic ICH patients were enrolled. For ICH cases, untreated hypertension was higher in blacks (43.6%, P<0.0001) and Hispanics (46.9%, P<0.0001) versus whites (32.7%). In multivariable analyses adjusted for alcohol use, anticoagulation, hypercholesterolemia, education, and medical insurance status, treated hypertension was a significant risk factor across all locations of ICH in whites (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.24-1.98; P<0.0001), blacks (OR, 3.02; 95% CI, 2.16-4.22; P<0.0001), and Hispanics (OR, 2.50; 95% CI, 1.73-3.62; P<0.0001). Untreated hypertension was a substantially greater risk factor for all 3 racial/ethnic groups across all locations of ICH: whites (OR, 8.79; 95% CI, 5.66-13.66; P<0.0001), blacks (OR, 12.46; 95% CI, 8.08-19.20; P<0.0001), and Hispanics (OR, 10.95; 95% CI, 6.58-18.23; P<0.0001). There was an interaction between race/ethnicity and ICH risk (P<0.0001).ConclusionsUntreated hypertension confers a greater ICH risk in blacks and Hispanics relative to whites across all anatomic locations of ICH. Accelerated research efforts are needed to improve overall hypertension treatment rates and to monitor the impact of such efforts on racial/ethnic disparities in stroke.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01202864.

Dataset Information

Variation in the maternal corticotrophin releasing hormone-binding protein (CRH-BP) gene and birth weight in Blacks, Hispanics and Whites.

Background

Methods

Results

Conclusions

Publications

Variation in the maternal corticotrophin releasing hormone-binding protein (CRH-BP) gene and birth weight in Blacks, Hispanics and Whites.

Similar Datasets

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