title: Altered transmission of maternal angiotensin II receptor haplotypes in fetal growth restriction.
abstract: Fetal growth restriction (FGR) predisposes to significant short- and long-term health problems. Epidemiological studies have suggested a role for inherited factors in its pathogenesis. The angiotensin II receptor genes, AGTR1 and AGTR2, are candidate genes because they mediate processes that are important for placentation. This study investigated AGTR1 and AGTR2 haplotypes and genotypes in FGR. A total of 107 families (father, mother, and baby) with FGR, and 101 families with normal pregnancies were genotyped at five sites in AGTR1 and six sites across AGTR2. All of the participants were white western Europeans. FGR was identified antenatally by ultrasound scans and confirmed postnatally by correcting the birth weight centile for gestation, infant sex, maternal height, weight, and parity. Fetal genes were investigated using transmission disequilibrium testing (TDT), and a case-control comparison of maternal haplotypes was conducted. FGR was associated with maternal (but not paternal) transmission of the AGTR1 haplotype (GenBank AF245699.1) g.4955T, g.5052T, g.5245C, g.5612A, and haplotype g.4955T, g.5052T, g.5245T, g.5612A. Haplotype g.4955A, g.5052G, g.5245T, g.5612G was undertransmitted (P = 0.002). TDT of the AGTR1 genotype showed undertransmission of maternal AGTR1 genotypes g.4955T>A (odds ratio (OR), 0.34 (95% confidence interval (CI), 0.14-0.86); P = 0.02), g.5052T>G (OR, 0.18 (0.06-0.48); P<0.001), and g.5612A>G (OR, 0.21 (0.08-0.55); P < 0.001) in FGR. There were no differences in maternal haplotype frequencies between normal pregnancy and FGR for AGTR1 or AGTR2 (P > 0.10). This is the first study to show distortion of transmission of maternal AGTR1 haplotypes in FGR, which suggests that this gene plays a role in FGR. In particular, maternal-fetal gene sharing may be an important factor.
authors.affiliation: Division of Clinical Chemistry, Institute of Genetics, School of Molecular Medical Sciences, University Hospital, Nottingham, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Tower
authors.forename: Sally
authors.initials: S
authors.lastname: Chappell
authors.forename: Meera
authors.initials: M
authors.lastname: Acharya
authors.forename: Richard
authors.initials: R
authors.lastname: Crane
authors.forename: Stephanie
authors.initials: S
authors.lastname: Szolin
authors.forename: Lyneth
authors.initials: L
authors.lastname: Symonds
authors.forename: Helen
authors.initials: H
authors.lastname: Chevins
authors.forename: Noor
authors.initials: N
authors.lastname: Kalsheker
authors.forename: Philip
authors.initials: P
authors.lastname: Baker
authors.forename: Linda
authors.initials: L
authors.lastname: Morgan
mesh_terms: D000328:Adult; D005192:Family Health; D005260:Female; D005317:Fetal Growth Retardation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic; D010641:Phenotype; D011247:Pregnancy; D011945:Receptors, Angiotensin / Q000235:genetics*; D012737:Sex Factors
chemical_list: D011945:Receptors, Angiotensin