title: Association of HLA-G alleles and 3' UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples.
abstract: Human leukocyte antigen (HLA)-G expression is restricted, expressed on trophoblast, with a major role in fetus acceptance. In addition to the 46 HLA-G alleles, the presence or absence of a 14 bp polymorphism located in the 3' UTR contributes to gene polymorphism that may influence both HLA-G mRNA stability and HLA-G isoform's splicing and consequently could play an immunomodulatory function in pregnancy. To elucidate the role of HLA-G polymorphism in pregnancy, HLA-G allele frequencies and the 14 bp polymorphisms were analyzed and compared in 60 couples with recurrent miscarriage (RM) and 68 fertile control couples. Two haplotypes showed a significant elevated frequency in patients (HLA-G*01:01:08/+14, p(c) < 0.0001 and HLA-G*01:04:01/-14, p(c) < 0.0001). The haplotype HLA-G*01:01:A/+14 exhibited a significant protective effect against RM in women (p(c) = 0.0238). Remarkably, significant differences in linkage disequilibrium were observed between patient and control groups. Two alleles showed a positive association with the +14 bp segment in RM patients and a strong negative association with fertile controls (HLA-G*01:01:08 = patients D' = 0.295-0.371; controls D' = -0.715 to -1.000; HLAG* 01:05N = patients D' = 0.728-1.000; controls D' = -1.000). HLA-G*01:04:01 showed a negative association with the 14 bp segment in patients and a positive association in controls (patients D' = -0.249 to - 0.674; controlss D' = 0.688-1.000). Our results suggest that haplotypic combinations of HLA-G alleles and the 14 bp segment may be associated with RM.
authors.affiliation: Immunogenetics and Histocompatibility Laboratory, Genetics Department, Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: Rafael Gustavo
authors.initials: RG
authors.lastname: Vargas
authors.forename: Paulo Roberto
authors.initials: PR
authors.lastname: Sarturi
authors.forename: Sibelle Botogosque
authors.initials: SB
authors.lastname: Mattar
authors.forename: Eni Piccioni
authors.initials: EP
authors.lastname: Bompeixe
authors.forename: Joandrei dos Santos
authors.initials: Jdos S
authors.lastname: Silva
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pirri
authors.forename: Maria da Graça
authors.initials: Mda G
authors.lastname: Bicalho
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000026:Abortion, Habitual / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D001938:Brazil; D004252:DNA Mutational Analysis; D005191:Family Characteristics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D006239:Haplotypes / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D011247:Pregnancy
chemical_list: D020413:3' Untranslated Regions; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I