Kahraman Cigdem Yuce, Tasdemir Sener, Sahin Ibrahim, Marzioglu Ozdemir Ebru, Yaralı Oguzhan, Ziypak Tevfik, Adanur Senol, Kahraman Mustafa, Tatar Abdulgani
1 Department of Medical Genetics, Erzurum Regional and Training Hospital , Erzurum, Turkey .
2 Department of Medical Genetics, Ataturk University Medical Faculty , Erzurum, Turkey .
Genet Test Mol Biomarkers. 2016 Apr;20(4):191-6. doi: 10.1089/gtmb.2015.0294. Epub 2016 Feb 11.
Varicocele is an abnormal enlargement of the pampiniform venous plexus in the scrotum. Varicocele is the most common cause of secondary male infertility. Nitric oxide (NO), which has a role on varicocele pathophysiology, is synthesized by endothelial nitric oxide synthase gene (NOS3).
In our study, we aimed to explain the relationship between varicocele, three common NOS3 polymorphisms (T-786C, G894T, 4b/a), and NOS3 mRNA expression levels.
We investigated NOS3 T-786C, G894T, and 4b/a polymorphisms in 102 patients with varicocele and 100 healthy controls. Twenty-four patients and 17 controls were chosen for expression studies based on polymorphism subgroupings. Subgroup 1 includes patients who have no minor allele polymorphisms, and subgroups 2, 3, and 4 have T-786C, G894T, and 4b/a polymorphisms, respectively.
The 4b/a polymorphism demonstrated significantly elevated levels in both allele and genotype analysis in the control group compared to the patient group. The G894T polymorphism was statistically elevated for genotypic frequencies in the patient group compared to the control group, but this finding did not extend to allelic frequencies. There were no statistically significant differences in either the allelic or genotypic frequencies between patients and control groups for the T-786C polymorphism. When patient and control expression levels were compared without considering the subgroups, the NOS3 expression level was found to be statistically higher in the patient group. There were no statistically significant differences in the patient and control group expression levels when stratified by subgroup, nor was there any effect of the polymorphisms under study on expression levels.
The 4b/a polymorphism may have a protective effect for varicocelem and G894T polymorphism may contribute to varicocele occurrence by lowering the level of NO. The higher NOS3 expression levels in the patient group may be a kind of dilator compensatory mechanism to protect vascular anatomy in varicocele.
精索静脉曲张是阴囊内蔓状静脉丛的异常扩张。精索静脉曲张是继发性男性不育的最常见原因。一氧化氮（NO）在精索静脉曲张的病理生理过程中起作用，它由内皮型一氧化氮合酶基因（NOS3）合成。
在我们的研究中，我们旨在解释精索静脉曲张、三种常见的NOS3基因多态性（T-786C、G894T、4b/a）与NOS3 mRNA表达水平之间的关系。
我们调查了102例精索静脉曲张患者和100例健康对照者的NOS3 T-786C、G894T和4b/a基因多态性。根据基因多态性亚组选择24例患者和17例对照进行表达研究。亚组1包括没有次要等位基因多态性的患者，亚组2、3和4分别具有T-786C、G894T和4b/a基因多态性。
与患者组相比，对照组在等位基因和基因型分析中4b/a基因多态性水平显著升高。与对照组相比，患者组G894T基因多态性的基因型频率在统计学上升高，但这一发现未扩展到等位基因频率。T-786C基因多态性在患者组和对照组之间的等位基因或基因型频率上均无统计学显著差异。在不考虑亚组的情况下比较患者和对照的表达水平时，发现患者组的NOS3表达水平在统计学上更高。按亚组分层时，患者组和对照组的表达水平无统计学显著差异，所研究的基因多态性对表达水平也没有任何影响。
4b/a基因多态性可能对精索静脉曲张有保护作用，G894T基因多态性可能通过降低NO水平导致精索静脉曲张的发生。患者组中较高的NOS3表达水平可能是一种扩张性补偿机制，以保护精索静脉曲张中的血管解剖结构。
