Heidari Mohammad Mehdi, Danafar Amirhossein, Moezzi Fahime, Khatami Mehri, Talebi Ali Reza
Department of Biology, Faculty of Science, Yazd University Yazd Iran.
Department of Biology, Ashkezar Islamic Azad University AshkezarYazd Iran.
Int J Reprod Biomed. 2019 Sep 3;17(8):557-566. doi: 10.18502/ijrm.v17i8.4821. eCollection 2019 Aug.
Numerous researches have provided great evidence that revealed the relationship between varicocele and sperm DNA damage.
Because of the crucial role of nuclear transition proteins (TPs) in sperm DNA condensation and integrity, this case-control study was designed to study gene nucleotide variations in Iranian patients with varicocele.
PCR-SSCP and DNA sequencing were used to search for mutations in exons 1 & 2 of the gene in 156 infertile patients with varicocele and 150 fertile men.
The results of sequencing showed three variants at positions c.301C░>░T (p.R101C), c.391C░>░T (p.R131░W), and g.IVS1-26G░>░C (rs8043625) of gene. It was found that varicocele risk in men who have the CC genotype of g.IVS1-26G░>░C SNP is higher than those who don't have these genotypes (according to Co-dominant model, Dominant model, Recessive model, and Over-dominant model). The haplotype-based analysis showed that (C/C/T) and (C/T/T) haplotypes were a risk factor of in patients with varicocele compared to controls (OR░=░3.278, p░=░0.000 and OR░=░9.304, p░=░0.038, respectively).
Because of the significant difference in the genotype and allele frequencies of g.IVS1-26G░>░C SNP in the intronic region of in patients with varicocele compared with controls and also because of the high conservation of this SNP position during evolution, this SNP may be involved in some important processes associated with the expression of this gene like mRNA splicing, but the exact mechanism is not clear.
大量研究提供了充分证据，揭示了精索静脉曲张与精子DNA损伤之间的关系。
由于核过渡蛋白（TPs）在精子DNA浓缩和完整性方面的关键作用，本病例对照研究旨在研究伊朗精索静脉曲张患者的基因核苷酸变异。
采用聚合酶链反应-单链构象多态性（PCR-SSCP）和DNA测序技术，对156例精索静脉曲张不育患者和150例有生育能力的男性的该基因外显子1和2进行突变检测。
测序结果显示该基因在c.301C＞T（p.R101C）、c.391C＞T（p.R131W）和g.IVS1-26G＞C（rs8043625）位点有三个变异。发现g.IVS1-26G＞C单核苷酸多态性（SNP）的CC基因型男性患精索静脉曲张的风险高于非该基因型男性（根据共显性模型、显性模型、隐性模型和超显性模型）。基于单倍型的分析表明，与对照组相比，（C/C/T）和（C/T/T）单倍型是精索静脉曲张患者的危险因素（优势比分别为3.278，p = 0.000和9.304，p = 0.038）。
精索静脉曲张患者与对照组相比，该基因内含子区域g.IVS1-26G＞C SNP的基因型和等位基因频率存在显著差异，且该SNP位点在进化过程中高度保守，因此该SNP可能参与了与该基因表达相关的一些重要过程，如mRNA剪接，但其确切机制尚不清楚。
