BMP4 circulating levels and promoter (rs17563) polymorphism in risk prediction of idiopathic male infertility.

INTRODUCTION: Bone morphogenetic proteins (BMPs) play an important role in the survival and proliferation of murine germ cells during embryonic development and the regulation of postnatal primordial germ cells migration. We hypothesised a link between BMP4 promoter (rs17563) gene polymorphism and its circulating levels with idiopathic male infertility.

METHODS: One hundred idiopathic infertile men and 126 fertile men were recruited. DNA was extracted from peripheral blood and genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The serum level of BMP4 was measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS: The C/C genotype was linked with a higher risk of idiopathic male infertility when compared with that of the T/T genotype (OR=4.84; 95%CI = 2.04-11.49; p=0.003). The recessive genetic model revealed a significantly increased risk of idiopathic male infertility in C/C genotype carriers when compared with that of the T/T and T/C genotypes (OR=5.45, 95%CI=2.35-12.65, p=0.001). The C allele was overrepresented in cases (36% versus 22%, in controls) leading to 2-fold increase risk of idiopathic male infertility (OR=2.01; 95%CI=1.32-3.05; p=0.001). There was is a significant decrease in serum BMP4 expression in infertile men as compared to controls (P=007).

CONCLUSION: BMP4 gene polymorphism and its circulating levels is related to idiopathic male infertility.