Association of Functional Genetic Variations in Uric Acid Transporters with the Risk of Idiopathic Male Infertility: A Genetic Association Study and Bioinformatic Analysis.

IF 2.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical Genetics Pub Date : 2024-08-14 DOI:10.1007/s10528-024-10902-6

Mohammad Karimian, Maryam Shabani, Hossein Nikzad

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引用次数: 0

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.

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尿酸转运体功能基因变异与特发性男性不育风险的关系：遗传关联研究与生物信息学分析》。

尿酸在维持和改善精子形态、存活率和活力方面发挥着重要作用。众所周知，SLC2A9 和 ABCG2 蛋白是主要的尿酸盐转运体，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，还研究了这些 SNP 与不育男性精浆中尿酸水平的相关性。随后，还进行了硅分析。在一项病例对照研究中，共招募了 193 名不育症患者和 154 名健康对照者。采集精液样本后，使用商业试剂盒测定精浆中的尿酸水平。从精子样本中提取基因组 DNA 后，采用 PCR-RFLP 方法进行 SNPs 基因分型。最后，利用生物信息学工具评估了 SNPs 对 SLC2A9 和 ABCG2 基因功能的影响。遗传关联研究显示，rs16890979、rs3733591、rs2231142 和 rs2231137 基因变异与男性不育风险增加之间存在显著关联。此外，这些变异还与少精子症和畸形精子症有关，有时还与无精子症有关。此外，我们还发现所研究的四个 SNPs 与畸形精子症和无精子症患者精浆中尿酸水平的降低有关。生物信息分析表明，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 基因变异可通过干扰精浆中的尿酸水平而被视为男性不育症的遗传风险因素。

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来源期刊

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.