DMRT1, RBMY, and AZFb genes polymorphism and expression role in azoospermia susceptibility

Male infertility can occur due to spermatogenesis defects. The most common causes of male infertility are azoospermia and oligospermia, which have several underlying factors, one of which is genetic. This study aimed to investigate the association of azoospermia with the DMRT1 and RBMY1A1 genes polymorphisms and AZFb region microdeletions in Iranian men. Moreover, these genes expression were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). A total of 100 Iranian men with azoospermia, oligozoospermia, or severe oligozoospermia and 100 fertile controls were included in this case-control study. A total of 200 subjects were genotyped for DMRT1 rs755383 and RBMY1A1 rs1481942953 polymorphisms using Tetra-ARMS PCR. The presence of two sequence-tagged sites (STS) markers from the Y chromosome AZFb region was also investigated by multiplex PCR. RT-PCR was used to analyze the expression in the testis tissue of azoospermia patients. With a P-value of 0.038, rs755383 in the DMRT1 gene was associated with an increased risk of azoospermia. However, no significant difference was found in genotype distribution in the RBMY1A1 (rs1481942953) gene polymorphism. Four patients showed Y chromosome microdeletions with sY127 and sY134 markers in the AZFb region. Infertile males' cDNA analysis revealed low expression levels for DMRT1 and PRY (one of the main genes in the AZFb region) with a p-value<0.0001. In contrast, RBMY1A1 expression level did not differ between patients and control groups with a p-value of 0.112. A receiver operating characteristic (ROC) curve analysis was carried out to detect genes with biomarker potential. With AUCs of 83% and 77%, DMRT1 and PRY had diagnostic marker potential in azoospermia detection.