ESTUDO DA ASSOCIAÇÃO DOS GENES HLA-A*, -B* E -DRB1* EM MULHERES COM ABORTAMENTO ESPONTÂNEO RECORRENTE (AER)

Abstract

Recurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous pregnancy losses before the 20th week of gestation, a situation that occurs in 1 to 2% of women in reproductive age. Genetic, anatomical, endocrine, infectious and immunologic factors through mechanisms that relate to the Major Histocompatibility Complex (MHC) and the presence of certain HLA (Human Leukocyte Antigens) are associated to RSA. HLA gene is located on the short arm of chromosome 6 between the 6p21.31 and 6p21.33 regions. This gene is inherited in haplotypes and expressed in codominance, having influence on modulation and induction of mother tolerance during the pregnancy. The aim of this study was to compare the allelic frequencies of HLA-A*, HLA-B* and HLA-DRB1* loci in women with and without RSA. It was a case-control study in 200 women (100 for each group) between 18 and 35 years of age. All samples were typified by the PCR-SSOP method (Polymerase Chain Reaction-Sequence Specific Oligonucleotide Probes). The most frequent alleles observed in the group of women with and without RSA were: HLAA* 02 (56%) and (49%), HLA-DRB1*13 (31%) and (39%) respectively - there was no statistical significative difference when compared among the groups for this alleles; HLA-A*24 (12%) e (25%), (OR: 0.41; 95% CI: 0.18-0.92; p=0.028); HLA-A*34 (8%) e (1%), (OR: 8.61; 95% CI: 1.06-187.04; p=0.034); HLA-B*35 (16%) e (41%) (OR: 0.27; 95% CI: 0.13 0.56; p=0.0002). The most frequent haplotypes observed in the group of women with and without RSA were: A*02DRB1*16 (12%) e (2%) (OR: 6.68; 95% CI: 1.36 44.52; p=0.012) respectively. In this research, DRB1* locus in women with RSA was in linkage disequilibrium (p=0.01.). The high frequency of HLA-A*02 and HLA-DRB1*13 alleles in this study was due to the wide distribution of this allele in the population of Maranhão. HLA-A*24 e HLA-B*35 alleles were considered as a protection factor and HLA-A*34 allele was considered as a risk factor to RSA. The A*02DRB1*16 haplotype was the most frequent and considered as a risk factor to RSA. In order to confirm the observed results in this research, a study involving a higher sample size is necessary as well as genetic epidemiology researches to shed light on the role of HLA antigens and/or its connection to other genes as a risk factor.