Association of the -308G/A Polymorphism of TNF-α Gene with Some Semen and Sperm Parameters in Men with Infertility

Abstract

Background The tumor necrosis factor alpha (TNF-α) gene is a cytokine involved in systemic inflammation. Results of the association of its polymorphisms with infertility in men are controversial. Objective The aim of this study was to evaluate the association of -308G/A polymorphism in TNF-α gene with different parameters of semen and sperm in infertile men. Methods Participants were 210 men with infertility and 120 controls. The polymorphism evaluation was performed by sequencing method. In order to assess oxidative stress and apoptosis in men with -308G/A polymorphism, malondialdehyde and caspase-9 values were measured. The sperm DNA damage and sex chromosomes aneuploidy were also measured in these patients. Findings A significant higher frequency of A allele of -308G/A polymorphism was observed in men with oligoasthenospermia (P=0.01). In semen samples of the men with AA genotype, there was significantly high level of malondialdehyde and caspase-9 (P<0.0001). We also observed higher frequency of sperm DNA damage (P=0.0001) and sex chromosome disomy type XY (P=0.0001) in sperm samples of men with AA genotype of -308G/A polymorphism. Furthermore, there was a significant correlation between sex chromosome aneuploidy and sperm DNA damage in sperms of men with this polymorphism (R=0.72, P=0.048). Conclusion -308G/A polymorphism of TNF-α gene has association with decreased sperm parameters, increased oxidative stress, higher sperm DNA damage and sex chromosome aneuploidy which can affect infertility.

Keywords

• male infertility
• tnf-α polymorphism
• oxidative stress
• sperm dna damage