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

Male infertility can occur due to spermatogenesis defects. The most common reasons for male infertility are azoospermia and oligospermia, which have several underlying factors, one of which is genetic. This study was aimed to investigate the association of azoospermia with the DMRT1 and RBMY1A1 genes polymorphisms and AZFb region microdeletions in Iranian men. Expression of these genes was assessed by 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. Subjects were genotyped for DMRT1 rs755383 and RBMY1A1 rs1481942953 polymorphisms using Tetra-ARMS PCR. The existence of two sequence-tagged sites (STSs) on the AZFb region was also investigated by multiplex PCR. RT-PCR was used to analyze the expression in the testis of azoospermia cases. With a p-value of 0.038, rs755383 in the DMRT1 gene was related to an elevated risk of azoospermia. However, no significant difference was found in genotype distribution in the RBMY1A1 (rs1481942953) gene polymorphism. Four cases demonstrated Y chromosome microdeletions with sY127 and sY134 markers. 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. ROC curve analysis was done to detect genes with biomarker potential. With AUCs of 83% and 77%, DMRT1 and PRY had diagnostic marker potential in azoospermia detection.