title: Smoking attenuated the association between IκBα rs696 polymorphism and defective spermatogenesis in humans.
abstract: Defective spermatogenesis is prevalent in infertile men, but the molecular mechanisms underlying its aetiology are largely unknown. In this study, a proposed association between IκBα SNPs, smoking-related ROS and sperm quality was investigated. Two polymorphisms in the IκBα gene, rs2233406 and rs696 were genotyped in 342 controls and 338 patients with defective spermatogenesis from a southern Chinese population. The results showed the rs696 AA genotype to be significantly more common (21.60% versus 14.33%, P = 0.013) and the rs696 GG genotype to be significantly rarer (28.99% versus 37.13%, P = 0.024) in the cases than in the controls. After subjects were stratified into smokers and nonsmokers, these differences were only observed in nonsmokers. Further analysis showed the rs696 AA genotype to be significantly closely associated with defective spermatogenesis in all subjects (P = 0.014, OR = 1.647) and in nonsmokers (P = 0.036, OR = 1.889). In a TM3 cell model, exposure to cigarette smoke condensate was found to activate NF-κB luciferase activity and altered transcriptional level of NF-κB pathway genes. In conclusion, this study demonstrates an association between functional polymorphisms of the IκBα rs696 and cigarette smoking with the risk of defective spermatogenesis, suggesting some interaction between the NF-κB signalling pathway and smoking-related ROS in human spermatogenesis.
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: Yu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: T
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Bai
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education in China, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000328:Adult; D000818:Animals; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D053627:Asthenozoospermia / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D002681:China / Q000453:epidemiology; D015870:Gene Expression / Q000187:drug effects; D059647:Gene-Environment Interaction; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics; D009845:Oligospermia / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017382:Reactive Oxygen Species; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055101:Semen Analysis; D015398:Signal Transduction / Q000235:genetics; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000453:epidemiology*; D013076:Sperm Count; D013081:Sperm Motility; D013091:Spermatogenesis / Q000187:drug effects; D014026:Nicotiana / Q000009:adverse effects
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D017382:Reactive Oxygen Species; D012906:Smoke; D000072000:NF-KappaB Inhibitor alpha
keywords: Cigarette smoking; IκBα; NF-κB; ROS; defective spermatogenesis