title: Cigarette smoking is associated with human semen quality in synergy with functional NRF2 polymorphisms.
abstract: Although cigarette smoking is considered a major risk factor for several human diseases, the effects of smoking on male fertility are controversial. Studies on the consequences of smoking, which also take into account genetic background, may facilitate understanding of the interactions between genes and smoking and their effects on male fertility. In this study, genetic variants of two functional polymorphisms of erythroid 2-related factor 2 (NRF2), mRNA expression levels of the antioxidant gene NRF2, catalase (CAT), superoxide dismutase isoenzyme-2 (SOD2), glutathione S-transferase-M1 (GSTM1), and seminal SOD activities were compared in 314 heavy smokers and 314 matched nonsmokers. The NRF2 rs6721961 TT genotype was found to be associated with low semen quality in heavy smokers (OR [95% CI] = 2.370 [1.106-5.081]). This variant genotype was found more frequently in heavy smokers with low semen quality than in those with high semen quality (P = 0.011). Heavy smokers with this genotype had significantly lower sperm concentrations and sperm counts (P < 0.05) when compared with those without this genotype. Smoking was also significantly associated with decreased seminal SOD activity (P < 0.05) and reduced NRF2 and SOD2 mRNA expression in heavy smokers with this variant genotype. These results were specific to heavy smokers with the NRF2 rs6721961 TT genotypes, but did not apply to nonsmokers or heavy smokers that did not carry this genotype. This study suggests an association between cigarette smoking in heavy smokers with NRF2 rs6721961 TT genotype and a decrease in semen quality.
authors.affiliation: Key Laboratory for Reproductive Medicine of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. yubolan@gmail.com
authors.forename: Bolan
authors.initials: B
authors.lastname: Yu
authors.forename: Jingyi
authors.initials: J
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Weiwei
authors.initials: W
authors.lastname: Xiao
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xia
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012661:Semen / Q000201:enzymology; D055101:Semen Analysis; D012907:Smoking / Q000009:adverse effects*; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000201:enzymology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D013482:Superoxide Dismutase
keywords: NRF2; semen quality; smoking; spermatogenesis; synergetic effect