HLA‐G polymorphism and in vitro fertilization failure in a Polish population

Abstract

To investigate whether human leukocyte antigen-G (HLA-G) gene polymorphism is associated with in vitro fertilization (IVF) failure, we sequenced exons 2-4 of the HLA-G gene in 50 couples with three or more IVFs (including 10 couples with five or more IVFs) and 58 control fertile couples from a Polish population. Of the 10 different HLA-G alleles identified in our study subjects, neither allele was found to be associated with IVF. We also genotyped 50 couples with IVF and 71 control couples for the -725C>G variant in the promoter region and the 14 bp insertion or deletion polymorphism in the 3' untranslated region of the HLA-G gene. The frequency of -725GG or GC genotype in women with IVF and in control fertile women was similar [26% vs 25.3%; odds ratio (OR) = 1.0; P = 1.0]. The 14 bp ins/ins or ins/del genotype was more common in women with IVF than in control women (76.9% vs 59.1%; OR 2.4; P = 0.03), but the difference was not significant after Bonferroni correction for multiple comparisons. The frequency of the ins/ins or ins/del genotype was particularly high (90%) in women who experienced five or more IVFs (OR = 6.2; P = 0.08), but again, the excess was not statistically significant, possibly because of small sample sizes. These results are in line with functional studies that show lower levels of HLA-G mRNA and protein related to the HLA-G allele including the 14 bp sequence and suggest that the insertion allele may be associated with an increased risk of IVF.

Human leukocyte antigen-G polymorphism in relation to expression, function, and disease

“…Some studies have reported an association between the ϩ14 bp/ϩ14 bp HLA-G genotype or the ϩ14-bp HLA-G allele in women and risk of RSA [62][63][64] or unsuccessful in vitro fertilization treatment [63,65]. A study by Tripathi and co-workers indicated a significant increase in the number of heterzygotes for the 14-bp polymorphism in RSA women versus control women [66].…”

HLA-G regulatory haplotypes and implantation outcome in couples who underwent assisted reproduction treatment

“…reviews 17 studies that have reported on the 14-bp ins/del polymorphism in exon 8 of HLA-G and its association with various pregnancy complications. Out of five studies that focused on recurrent spontaneous abortion (RSA) [8,9,[11][12][13], four reported a link with mRNA expression [14][15][16][17], four with pre-eclampsia [10,18,19], three with IVF treatment [20][21][22] and one with birth weight [23].…”

Simple Methods for the Detection of HLA-G Variants in Coding and Non-coding Regions

“…allele HLA-G*01:01 only 4 out of the 33 SNPs within the coding region of HLA-G are related to an amino acid exchange, which do present frequencies above 1% in population studies (4)(5)(6)(7)(8)(9) . One of them is located at codon 31 in exon 2 exchanging a threonine for serine, being typical for the G*01:03 allele (Table 1 ).…”