RESUMO
The role of HLA-G in several clinical conditions related to reproduction has been investigated. Important polymorphisms have been found within the 5'URR and 3'UTR regions of the HLA-G promoter. The aim of the present study was to investigate 16 SNPs in the 5'URR and 14-bp insertion/deletion (ins/del) polymorphism located in the 3'UTR region of the HLA-G gene and its possible association with the implantation outcome in couples who underwent assisted reproduction treatments (ART). The case group was composed of 25 ART couples. Ninety-four couples with two or more term pregnancies composed the control group. Polymorphism haplotype frequencies of the HLA-G were determined for both groups. The Haplotype 5, Haplotype 8 and Haplotype 11 were absolute absence in ART couples. The HLA-G*01:01:02a, HLA-G*01:01:02b alleles and the 14-bp ins polymorphism, Haplotype 2, showed an increased frequency in case women and similar distribution between case and control men. However, this susceptibility haplotype is significantly presented in case women and in couple with failure implantation after treatment, which led us to suggest a maternal effect, associated with this haplotype, once their presence in women is related to a higher number of couples who underwent ART.
Assuntos
Implantação do Embrião/genética , Antígenos HLA-G/genética , Haplótipos , Reprodução/genética , Adulto , Alelos , Feminino , Frequência do Gene , Humanos , Masculino , Polimorfismo Genético , Técnicas de Reprodução AssistidaRESUMO
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.
Assuntos
Regiões 3' não Traduzidas/genética , Aborto Habitual/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Aborto Habitual/epidemiologia , Aborto Habitual/fisiopatologia , Adulto , Brasil , Análise Mutacional de DNA , Características da Família , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Antígenos HLA-G , Haplótipos/genética , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo Genético , GravidezRESUMO
The new human leukocyte antigen (HLA) class I allele, HLA-A*0355 was identified in a Brazilian family. Our sequence analysis detected a mismatch located in exon 2, codon 86, at position 258 (C-->A) that results in a nonsilent and nonconservative substitution with the replacement of asparagine by lysine. Substitutions located at this oligosaccharide attachment site of the protein were observed in only other four classic HLA class I sequences, indicating a highly conserved peptide site however its function remains unknown.
Assuntos
Alelos , Antígenos HLA-A/genética , População Branca/genética , Adulto , Substituição de Aminoácidos/genética , Sequência de Bases/genética , Brasil , Clonagem Molecular , Europa Oriental/etnologia , Feminino , Genótipo , Antígeno HLA-A2 , Antígeno HLA-A3 , Haplótipos , Teste de Histocompatibilidade , Humanos , Dados de Sequência Molecular , Análise de Sequência de DNA , IrmãosRESUMO
PROBLEM: Natural killer (NK) cells are regulated through NK cell receptors such as killer cell immunoglobulin-like receptors (KIRs). KIRs are suspected of being involved in the causes of recurrent miscarriage (RM) as a higher proportion of activated NK cells were observed in women with RM when compared with that in controls. The aim of this study was to investigate if KIR genes coding for receptors known to have as ligands HLA class I molecules are correlated with RM. METHOD OF STUDY: A matched case-control study was carried out in 68 south Brazilian Caucasian patient couples with RM and 68 control fertile couples. KIR genes were typed by PCR-Reverse SSO method. RESULTS: The rate of possession of an elevated number of activating KIR genes (positive for five or six activating KIR genes out of six different activating KIR genes analyzed) in RM patient women was significantly higher (P = 0.0201) when compared with that in control fertile women. These data suggest that women carrying a high content of activating KIR genes have about threefold increased probability to develop RM [OR = 2.71; 95% CI (1.23-6.01)]. CONCLUSION: Our results indicate that RM could be associated with NK cell activation mediated by a profile rich in activating KIR genes.
