title: Genetic variants in telomerase reverse transcriptase (TERT) and telomerase-associated protein 1 (TEP1) and the risk of male infertility.
abstract: 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.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yan
authors.affiliation: Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042, China.
authors.forename: Shengmin
authors.initials: S
authors.lastname: Wu
authors.affiliation: Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042, China.
authors.forename: Shenghu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China. Electronic address: aihuagu@njmu.edu.cn.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gu
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D053938:DNA Fragmentation; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins; D012306:Risk; D013094:Spermatozoa / Q000378:metabolism; D019098:Telomerase / Q000235:genetics*; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D016601:RNA-Binding Proteins; C104342:TEP1 protein, human; C509186:TERT protein, human; D019098:Telomerase
keywords: BMI; CI; DNA double-strand break; DSB; FDR; LD; MAF; Male infertility; OR; SNP; SNPs; TEP1; TERC; TERT; TUNEL; body mass index; confidence interval; false discovery rate; linkage disequilibrium; minor allele frequency; odds ratio; single nucleotide polymorphism; telomerase RNA component; telomerase reverse transcriptase; telomerase-associated protein 1; terminal-deoxynucleoitidyl transferase mediated nick end labeling