Vučić N L J, Nikolić Z Z, Vukotić V D, Tomović S M, Vuković I I, Kanazir S D, Savić-Pavićević D L J, Brajušković G N
Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
Special Urology Ordination "TTC", Belgrade, Serbia.
Andrologia. 2018 Feb;50(1). doi: 10.1111/and.12817. Epub 2017 May 3.
Results of recent studies confirmed that oxidative stress negatively affects sperm motility and causes sperm DNA damage. Produced by nitric oxide synthase 3 (NOS3), nitric oxide is considered to be one of the important mediators of oxidative stress in testis tissue. The aim of this study was to assess the possible association of three genetic variants (rs2070744, rs1799983 and intron variant 4a/4b) in NOS3 gene and infertility occurrence in two groups of infertile men (idiopathic azoospermia and oligoasthenozoospermia) and fertile controls. Genotypes for the single-nucleotide genetic variants rs1799983 and rs2070744 were determined by PCR-RFLP, while genotyping of intron 4 variant 4a/4b was performed by gel electrophoresis of PCR products. Statistical analysis was performed by SNPStats software. No significant association between the three genetic variants of the NOS3 gene and infertility risk was determined comparing allele and genotype frequencies among group of patients diagnosed with azoospermia and the control group. Nevertheless, there was a significant positive association between 4a/4b and infertility in the group of males diagnosed with oligoasthenozoospermia, under overdominant genetic model. Our findings suggest that tandem repeat variant within intron 4 of the NOS3 gene is associated with an increased risk of infertility in men diagnosed with idiopathic oligoasthenozoospermia.
近期研究结果证实，氧化应激会对精子活力产生负面影响，并导致精子DNA损伤。一氧化氮由一氧化氮合酶3（NOS3）产生，被认为是睾丸组织氧化应激的重要介质之一。本研究的目的是评估NOS3基因中的三种基因变异（rs2070744、rs1799983和内含子变异4a/4b）与两组不育男性（特发性无精子症和少弱精子症）及生育对照组中不育症发生之间的可能关联。通过PCR-RFLP确定单核苷酸基因变异rs1799983和rs2070744的基因型，而通过PCR产物的凝胶电泳对内含子4变异4a/4b进行基因分型。使用SNPStats软件进行统计分析。比较无精子症患者组和对照组之间的等位基因和基因型频率，未确定NOS3基因的三种基因变异与不育风险之间存在显著关联。然而，在超显性遗传模型下，在诊断为少弱精子症的男性组中，4a/4b与不育之间存在显著正相关。我们的研究结果表明，NOS3基因内含子4中的串联重复变异与诊断为特发性少弱精子症的男性不育风险增加有关。
