Mohammad Mehdi Heidari - Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.
Amirhossein Danafar - Department of Biology, Ashkezar Islamic Azad University, Ashkezar, Yazd, Iran.
Fahime Moezzi - Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.
Mehri Khatami - Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.
Ali Reza talebi - Research and Clinical Center for Infertility and Department of Anatomy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Background: Numerous researches have provided great evidence that revealed the relationship between varicocele and sperm DNA damage. Objective: Because of the crucial role of nuclear transition proteins (TPs) in sperm DNA condensation and integrity, this case-control study was designed to study TNP2 gene nucleotide variations in Iranian patients with varicocele. Materials and Methods: PCR-SSCP and DNA sequencing were used to search for mutations in exons 1 & 2 of the TNP2 gene in 156 infertile patients with varicocele and 150 fertile men. Results: 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 TNP2 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).Conclusion: Because of the significant difference in the genotype and allele frequencies of g.IVS1-26G > C SNP in the intronic region of TNP2 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.

Varicocele, Genetic polymorphism, Infertility, Nuclear transition protein 2.