The association between TNP2 gene polymorphisms and Iranian infertile men with varicocele: A case-control study|
Heidari, Mohammad Mehdi; Danafar, Amirhossein; Moezzi, Fahime; Khatami, Mehri & Talebi, Ali Reza
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,
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.