• PMID: 24269974
• Gene Name: TERT
• Condition: Male infertility
• Association: In conclusion, our results give the first evidence that genetic variations of TERT rs2736100 and TEP1 rs1713449 were associated with susceptibility to male infertility.
• Mutation: TERT rs2736100, TEP1 rs1713449
• Population size: 1160
• Population details: 1160 (580 male infertility cases, 580 matched controls)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: TERT rs2736100, TEP1 rs1713449
• Other associated phenotypes: Male infertility

Genetic variants in telomerase reverse transcriptase (TERT) and telomerase-associated protein 1 (TEP1) and the risk of male infertility

Yan L, Wu S, Zhang S, Ji G, Gu A.

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. CI - Copyright © 2013 Elsevier B.V. All rights reserved. FAU - Yan, Lifeng AU - Yan L AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China. FAU - Wu, Shengmin AU - Wu S AD - Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042, China. FAU - Zhang, Shenghu AU - Zhang S AD - Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042, China. FAU - Ji, Guixiang AU - Ji G AD - Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042, China. Electronic address: jgx@nies.org.