title: Polymorphism in maternal LRP8 gene is associated with fetal growth.
abstract: Fetal growth restriction (FGR) affects >200,000 pregnancies in the United States annually and is associated with increased perinatal mortality and morbidity, as well as poorer long-term health for infants with FGR compared with infants without FGR. FGR appears to be a complex trait, but the role of genetic factors in the development of FGR is largely unknown. We conducted a candidate-gene association study of birth weight and FGR in two independent study samples obtained at the Boston Medical Center. We first investigated the association between maternal genotypes of 68 single-nucleotide polymorphisms (SNPs) from 41 candidate genes and fetal growth in a sample of 204 black women selected for a previous study of preeclampsia, 92 of whom had preeclampsia (characterized by high blood pressure and the presence of protein in the urine). We found significant association between SNP rs2297660 in the LRP8 gene and birth weight. Subsequently, we replicated the association in a larger independent sample of 1,094 black women; similar association between LRP8 and FGR was observed in this sample. The "A" allele at rs2297660 was associated with a higher standardized birth weight and a lower risk of FGR. Under the additive genetic model, each additional copy of the "A" allele reduced the risk of FGR by 33% (P<.05). In conclusion, results from the two independent samples of black women provide consistent evidence that SNP rs2297660 in LRP8 is associated with fetal growth.
authors.affiliation: Program for Population Genetics, Harvard School of Public Health, Boston; Department of Human Genetics, University of California-Los Angeles, Los Angeles.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston.
authors.forename: Nan
authors.initials: N
authors.lastname: Laird
authors.affiliation: Department of Pediatrics, Boston University Medical Center, Boston.
authors.forename: Barry
authors.initials: B
authors.lastname: Zuckerman
authors.affiliation: Department of Obstetrics and Gynecology, Boston University Medical Center, Boston.
authors.forename: Philip
authors.initials: P
authors.lastname: Stubblefield
authors.affiliation: Program for Population Genetics, Harvard School of Public Health, Boston. Electronic address: xin_xu@harvard.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D005317:Fetal Growth Retardation / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000453:epidemiology / Q000235:genetics; D007231:Infant, Newborn; D026502:LDL-Receptor Related Proteins; D009035:Mothers; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000453:epidemiology / Q000235:genetics; D011247:Pregnancy; D018110:Receptors, Lipoprotein / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D026502:LDL-Receptor Related Proteins; D018110:Receptors, Lipoprotein; C098773:low density lipoprotein receptor-related protein 8