A tug-of-war between tolerance and rejection - New evidence for 3'UTR HLA-G haplotypes influence in recurrent pregnancy loss

• Published in: Human immunology 2016-10, Vol.77 (10), p.892-897
• Main Authors: Michita, Rafael Tomoya, Zambra, Francis Maria Báo, Fraga, Lucas Rosa, Sanseverino, Maria Teresa Vieira, Callegari-Jacques, Sidia Maria, Vianna, Priscila, Chies, José Artur Bogo
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Abortion, Habitual - genetics; Adolescent; Adult; African Continental Ancestry Group; Brazil; European Continental Ancestry Group; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Graft Rejection - genetics; Haplotypes; HLA-G Antigens - genetics; Humans; Polymorphism, Single Nucleotide; Pregnancy; Transplantation Tolerance - genetics; Young Adult
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2016.07.004

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.