title: A tug-of-war between tolerance and rejection - New evidence for 3'UTR HLA-G haplotypes influence in recurrent pregnancy loss.
abstract: HLA-G is a molecule essential to the maintenance of the maternal-fetal interface tolerance, thus contributing to a healthy pregnancy. Here we investigate the role of HLA-G single nucleotide polymorphisms (SNPs) and whether a specific HLA-G haplotype influence or not recurrent pregnancy loss (RPL) risk. A total of 296 DNA samples from RPL (N=140) and controls (N=156) were evaluated. The HLA-G 3'UTR region was sequenced and eight major SNPs were evaluated (14pb insertion/deletion, +3003T/C, +3010C/G, +3027C/A, +3035C/T, +3142G/C, +3187A/G, +3196C/G). A high linkage disequilibrium (LD) among all pairs and a perfect LD between +3010C/G and +3142G/A (D'=1.0, r(2)=1.0) were observed. Our data showed an increased risk to +3010CC genotype carriers in comparison with control [odds ratio (OR) 2.05 95% confidence interval (CI) 1.05-4.00, p=0.035] and to a decreased risk of RPL in +3142CC genotype carriers (OR=0.49 95%CI 0.25-0.95, p=0.035) and +3187AG genotype carriers (OR=0.58 95%CI 0.35-0.94, p=0.029). A total of eight haplotypes were observed in the sample, being UTR-1 and UTR-2 the most represented. An association between UTR-1 haplotype carriers with a reduced risk of both RPL and secondary RPL was observed. Our results indicate that the HLA-G 3'UTR plays important roles in RPL and might be an important marker of susceptibility to this, and possible to other, pregnancy disorders.
authors.affiliation: Genetics Department, Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Rafael Tomoya
authors.initials: RT
authors.lastname: Michita
authors.affiliation: Genetics Department, Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Francis Maria Báo
authors.initials: FMB
authors.lastname: Zambra
authors.affiliation: Genetics Department, Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Lucas Rosa
authors.initials: LR
authors.lastname: Fraga
authors.affiliation: Genetics Department, Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; National Institute of Science and Technology in Populational Medical Genetics (INAGEMP), Porto Alegre, RS, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors.forename: Maria Teresa Vieira
authors.initials: MTV
authors.lastname: Sanseverino
authors.affiliation: Department of Statistics, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Sidia Maria
authors.initials: SM
authors.lastname: Callegari-Jacques
authors.affiliation: Genetics Department, Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: Vianna
authors.affiliation: Genetics Department, Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. Electronic address: jabchies@terra.com.br.
authors.forename: José Artur Bogo
authors.initials: JAB
authors.lastname: Chies
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000026:Abortion, Habitual / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D044383:Black People; D001938:Brazil; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D059951:HLA-G Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D023001:Transplantation Tolerance / Q000235:genetics; D044465:White People; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens
keywords: 3′UTR; Abortion; HLA-G; Haplotype; Miscarriage; Polymorphism; Recurrent pregnancy loss