title: Genetic variants in Ser-Arg protein-coding genes are associated with the risk of nonobstructive azoospermia in Chinese men.
abstract: OBJECTIVE
  To evaluate the association between genetic variants in Ser-Arg (SR) protein-coding genes and the susceptibility of nonobstructive azoospermia (NOA) in Chinese men.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  State Key Laboratory of Reproductive Medicine in Nanjing Medical University conducted the genotyping and examined the expression levels of genes.
  
  
  METHODS
  The study included 962 NOA patients and 1,931 control subjects.
  
  
  METHODS
  None.
  
  
  METHODS
  Genotyping of 16 single-nucleotide polymorphisms (SNPs) of eight "canonic" SR protein-coding genes were performed with the use of the Illumina Infinium Beadchip platform. Odds ratios were calculated by logistic regression analysis in the additive model. Expression levels were measured by quantitative reverse-transcription polymerase chain reaction.
  
  
  RESULTS
  Rs17431717 near SFRS9 and rs12046213 near SFRS4 were significantly associated with a decreased risk of NOA, whereas rs10849753 near SFRS9 and rs6103330 in SFRS6 were associated with an increased risk of NOA. Of the two SNPs in SFRS9, only rs17431717 remained significant after conditioning on another. Combined analysis of three promising SNPs (rs17431717, rs12046213, and rs6103330) showed that compared with individuals with "0-2" risk alleles, those carrying "3," "4," and "≥ 5" risk alleles had 1.22-, 1.38-, and 1.90-fold increased risk of NOA, respectively.
  
  
  CONCLUSIONS
  Polymorphisms in SR protein-coding genes may contribute to the risk of NOA in Chinese men. The findings of this study can help us to further understand the etiology of spermatogenic impairment, and they provide more evidence for the role of splicing activity in human spermatogenesis.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China; Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Bixian
authors.initials: B
authors.lastname: Ni
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China; Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China; Department of Toxicology and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China; Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China. Electronic address: zhibin_hu@njmu.edu.cn.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000328:Adult; D053713:Azoospermia / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D005298:Fertility / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D012307:Risk Factors; D000068103:Serine-Arginine Splicing Factors; D013091:Spermatogenesis / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors
keywords: NOA; SR protein family; alternative splicing; susceptibility