title: rs189037, a functional variant in ATM gene promoter, is associated with idiopathic nonobstructive azoospermia.
abstract: OBJECTIVE
  To investigate the relationship between a functional variant rs189037(G>A) in ATM promoter and idiopathic nonobstructive azoospermia (INOA) in a Chinese population.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Medical academy and hospital.
  
  
  METHODS
  Two hundred twenty-nine INOA patients and 236 fertile male controls.
  
  
  METHODS
  None.
  
  
  METHODS
  Genotyping was performed by polymerase chain reaction-based restriction fragment length polymorphism and subsequently confirmed by DNA sequencing. Odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated for the risk genotype and allele. Bioinformatic analysis was also performed to predict the biological function of rs189037(G>A).
  
  
  RESULTS
  The AA genotype and A allele at rs189037(G>A) locus were both associated with an increased risk of INOA, with OR 1.90 (95% CI 1.214-3.007) for AA and 1.41 (95% CI 1.112-1.775) for A allele. The heterozygous GA and GA+AA had no relationship with INOA risk, with OR 1.06 (95% CI 0.761-1.472) and 1.28 (95% CI 0.954-1.708), respectively. Meanwhile, stratification by genotype showed that INOA patients with AA had higher FSH level, lower total T level, and smaller testicular size than those patients with GG. Furthermore, bioinformatic analysis predicted that the rs189037(G>A) variant was located in a well-conserved region in ATM promoter and that the transition of allele G to allele A might lead to differential allelic expression of ATM gene via modifying of the DNA-binding ability of transcription factor E2F1.
  
  
  CONCLUSIONS
  The genetic variant rs189037(G>A) in ATM gene promoter contributes to an increased risk of INOA in a Chinese population, possibly through affecting the DNA-binding ability of E2F1 and subsequent ATM expression.
authors.affiliation: Center for Reproductive Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang Province, People's Republic of China. Electronic address: zhongxiangli@gmail.com.
authors.forename: Zhongxiang
authors.initials: Z
authors.lastname: Li
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Hongchao
authors.initials: H
authors.lastname: Li
authors.forename: Ya
authors.initials: Y
authors.lastname: Ni
mesh_terms: D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D053713:Azoospermia / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM; Idiopathic nonobstructive azoospermia; genetic association; single-nucleotide polymorphism