Variation in Hyaluronan-Binding Protein 2 (HABP2) Promoter Region is Associated With Unexplained Female Infertility

Abstract

We set up to analyze polymorphisms in hyaluronan-binding protein 2 (HABP2) gene in healthy fertile women (n = 158) and in women with unexplained infertility (n = 116) and to investigate the potential role of HABP2 in receptive endometrium. Minor rs1157916 A and the major rs2240879 A alleles together with AA genotypes were significantly less frequent in infertile women than in controls. Immunohistochemistry analysis of endometrial HABP2 expression at the time of implantation identified significantly lower HABP2 protein level in infertile women in stroma and vessels than in fertile women. Migration assay analysis of cultured trophoblast and endothelial cells toward HABP2 protein referred to the function of HABP2 in endometrial endothelial cells. In conclusion, our results indicate that polymorphisms in the regulatory region of HABP2 gene could influence gene expression levels in the receptive endometrium and could thereby be one reason for infertility complications in women with unexplained infertility. Additionally, HABP2 protein involvement in endometrial angiogenesis is proposed.