Association of HLA-G alleles and 3' UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples

Rafael Gustavo Vargas, Paulo Roberto Sarturi, Sibelle Botogosque Mattar, Eni Piccioni Bompeixe, Joandrei dos Santos Silva, Alessandro Pirri, Maria da Graça Bicalho
Human Immunology 2011, 72 (6): 479-85
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.

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