Abstract：
Uric acid plays an important role in sustaining and improving sperm morphology, viability, and motility. It is known that SLC2A9 and ABCG2 protein are the main urate transporter and genetic variations in these genes could be associated with the levels of serum uric acid. This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) SLC2A9-rs16890979, SLC2A9-rs3733591, ABCG2-rs2231142, and ABCG2-rs2231137 with male infertility. Additionally, the correlation of these SNPs with the uric acid level in seminal plasma of infertile men was examined. Subsequently, an in silico analysis was performed. In a case-control study, 193 infertile and 154 healthy controls were recruited. After semen sample collection, the uric acid level of seminal plasma was measured by a commercial kit. After genomic DNA extraction from sperm samples, SNPs genotyping was performed by PCR-RFLP method. Lastly, the effects of SNPs on the SLC2A9 and ABCG2 gene function were evaluated by bioinformatics tools. The genetic association study revealed that there are significant associations between rs16890979, rs3733591, rs2231142, and rs2231137 genetic variations and increased risk of male infertility. Also, these variations were associated with oligozoospermia and teratozoospermia, and sometimes with asthenozoospermia. Also, we found that four studied SNPs could be associated with a decreased level of uric acid of seminal plasma in teratozoospermia and asthenozoospermia. Bioinformatic analysis revealed that the mentioned polymorphisms could affect molecular aspects of SLC2A9 and ABCG2 genes. In this preliminary study, the rs16890979, rs3733591, rs2231142, and rs2231137 genetic variations could be considered as genetic risk factors for male infertility by interfering with the uric acid level of seminal plasma.
摘要：
尿酸在维持和改善精子形态中起着重要作用，生存能力，和运动性。已知SLC2A9和ABCG2蛋白是主要的尿酸转运蛋白，这些基因的遗传变异可能与血清尿酸水平有关。本研究旨在探讨单核苷酸多态性（SNPs）SLC2A9-rs16890979、SLC2A9-rs3733591、ABCG2-rs2231142和ABCG2-rs2231137与男性不育的关系。此外,研究了这些SNP与不育男性精浆中尿酸水平的相关性。随后，进行了计算机模拟分析。在一项病例对照研究中，招募了193名不育者和154名健康对照者。精液样本采集后,通过商业试剂盒测量精浆的尿酸水平。从精子样本中提取基因组DNA后，通过PCR-RFLP方法进行SNP基因分型。最后,通过生物信息学工具评估SNP对SLC2A9和ABCG2基因功能的影响。遗传关联研究表明，rs16890979，rs3733591，rs2231142和rs2231137遗传变异之间存在显着关联，并且男性不育的风险增加。此外，这些变异与少精子症和畸形精子症有关，有时有弱精子症.此外，我们发现，4个研究的SNPs可能与畸形精子症和弱精子症中的精浆尿酸水平降低有关。生物信息学分析表明，上述多态性可能会影响SLC2A9和ABCG2基因的分子方面。在这项初步研究中，rs16890979，rs3733591，rs2231142和rs2231137遗传变异可通过干扰精浆尿酸水平而被认为是男性不育的遗传危险因素。
