Copyright © 2013 Elsevier B.V. All rights reserved.
Telomeres are critical in maintaining genomic stability and integrity, and telomerase expression in spermatogonial stem cells is responsible for the maintenance of telomere length in the human male germline. Genetic variants in telomere-associated pathway genes might affect telomere length and chromosomal stability, and subsequently disease susceptibility. Thus, we hypothesize that single nucleotide polymorphisms (SNPs) in this pathway could contribute to male infertility risk. In a case-control study of 580 male infertility cases and 580 matched controls, 8 common SNPs in telomerase reverse transcriptase (TERT) and telomerase-associated protein 1 (TEP1) were genotyped. Overall, we found that TERT rs2736100 was inversely associated with male infertility risk (adjusted odds ratio (OR)=0.66, 95% confidence interval (CI): 0.47-0.92; Ptrend=0.011), whereas TEP1 rs1713449 was positively associated with risk of male infertility (adjusted OR=1.39, 95% CI: 1.20-1.62; Ptrend<0.001). In addition, subjects carrying risk genotypes of these both loci had a two-fold (95% CI: 1.34-3.15) increase in the risk of male infertility, indicating a significant gene-gene interaction between these two loci (P for multiplicative interaction=0.009). Moreover, linear regression analysis showed that individuals carrying the TEP1 rs1713419 variants have significantly higher levels of sperm DNA fragmentation (β=2.243, P=0.016). In conclusion, our results give the first evidence that genetic variations of TERT rs2736100 and TEP1 rs1713449 were associated with susceptibility to male infertility.