Department of Medical Biology, School of Medicine, Ankara University, Ankara, Turkey.
Research Laboratories for Health Science, Y Gen Biotechnology Company Ltd, Ankara, Turkey.
Syst Biol Reprod Med. 2021 Dec;67(6):399-412. doi: 10.1080/19396368.2021.1972359. Epub 2021 Sep 19.
This study examines the association of the -617 C > A polymorphism in the Nrf2 gene (rs6721961) with male infertility in a Turkish population and determines its functional role in spermatogenesis in correlation with the impact of different levels of DNA damage on the genotypes. A total of 100 infertile men and 100 healthy fertile men were included in the study. Nrf2 genotyping was performed with the PCR-based restriction fragment length gene polymorphism (RFLP-PCR) analysis. According to our results, the Nrf2 CC, CA, and AA genotype distribution frequencies were 58.6%, 38.4%, and 3% in the control group, respectively, and 38%, 48%, and 14% in the infertile men, respectively. The AA genotype was significantly higher in the patient group. In smokers, a significant difference was found in progressive motility values between the genotypes (p = 0.001). Also, sperm progressive motility and concentration decreased significantly in those smokers with the AA genotype; smokers carrying this genotype were also 5.75 times more likely to have oligoasthenozoospermia than those with CC (p < 0.05). There was a significant relationship between the number of cases with high sperm-DNA damage when comparing the frequency of Nrf2 AA genotype carriers with the CC genotype 16.3% vs. 6.9%, respectively (p < 0.001). These results suggest the importance of the Nrf2 gene C > A (rs 6,721,961) polymorphism in the etiology of sperm DNA damage as a risk factor for male infertility. Smokers carrying the AA genotype are more likely to impair seminal parameters through antioxidant mechanisms.: Polymerase chain reaction (PCR)-based restriction fragment length gene polymorphism (RFLP-PCR); reactive oxygen species (ROS); deoxyribonucleic acid (DNA); catalases (CATs); superoxide dismutase (SOD); glutathione peroxidase (GPX); glutathione-S-transferase (GST); Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2); basic leucine zipper (bZIP); antioxidant response element (ARE); World Health Organization (WHO);normospermia(NS);asthenozoospermia(AS);oligozoospermia(OS);oligoasthenozoospermia (OAS); follicle stimulating hormone (FSH); ultraviolet (UV); low-melting-point agarose (LMA); normal-melting-point agarose (NMA); arbitrary units (AU); total comet score (TCS); A one-way analysis of variance (ANOVA); standard deviation (SD); N-acetyltransferase (NAT2); small non-coding RNAs (ncRNAs); microRNAs (miRNA).
本研究旨在探讨土耳其人群中 Nrf2 基因（rs6721961）-617C > A 多态性与男性不育之间的关联，并确定其在精子发生中的功能作用，同时关联不同水平的 DNA 损伤对基因型的影响。研究纳入了 100 名不育男性和 100 名健康生育男性。采用基于聚合酶链反应的限制性片段长度基因多态性（RFLP-PCR）分析进行 Nrf2 基因分型。根据我们的结果，对照组中 Nrf2 CC、CA 和 AA 基因型的分布频率分别为 58.6%、38.4%和 3%，而不育男性组中分别为 38%、48%和 14%。AA 基因型在患者组中显著升高。在吸烟者中，基因型之间的前向运动值存在显著差异（p = 0.001）。此外，AA 基因型的吸烟者精子前向运动和浓度显著下降；携带该基因型的吸烟者发生少精症和弱精症的可能性也比 CC 基因型高 5.75 倍（p < 0.05）。当比较 Nrf2 AA 基因型携带者与 CC 基因型携带者的高精子 DNA 损伤病例数的频率时，发现有显著关系，分别为 16.3%和 6.9%（p < 0.001）。这些结果表明，Nrf2 基因 C > A（rs6721961）多态性在精子 DNA 损伤的病因学中作为男性不育的危险因素具有重要意义。携带 AA 基因型的吸烟者通过抗氧化机制更有可能损害精液参数：聚合酶链反应（PCR）-基于限制性片段长度基因多态性（RFLP-PCR）；活性氧（ROS）；脱氧核糖核酸（DNA）；过氧化氢酶（CATs）；超氧化物歧化酶（SOD）；谷胱甘肽过氧化物酶（GPX）；谷胱甘肽-S-转移酶（GST）；核因子红细胞 2（NF-E2）相关因子 2（Nrf2）；碱性亮氨酸拉链（bZIP）；抗氧化反应元件（ARE）；世界卫生组织（WHO）；正常精子（NS）；弱精子症（AS）；少精子症（OS）；少弱精子症（OAS）；卵泡刺激素（FSH）；紫外线（UV）；低熔点琼脂糖（LMA）；普通熔点琼脂糖（NMA）；任意单位（AU）；总彗星评分（TCS）；单因素方差分析（ANOVA）；标准差（SD）；乙酰转移酶（NAT2）；小非编码 RNA（ncRNA）；微小 RNA（miRNA）。
