• PMID: 23993922
• Gene Name: E2F1
• Condition: Idiopathic nonobstructive azoospermia (INOA)
• Association: 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.
• Mutation: rs189037(G>A)
• Population size: 465
• Population details: 465 (229 INOA patients, 236 fertile male controls)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: ATM gene promoter, E2F1
• Other associated phenotypes: Idiopathic nonobstructive azoospermia (INOA)

rs189037, a functional variant in ATM gene promoter, is associated with idiopathic nonobstructive azoospermia

Li Z, Yu J, Zhang T, Li H, Ni Y.

OBJECTIVE: To investigate the relationship between a functional variant rs189037(G>A) in ATM promoter and idiopathic nonobstructive azoospermia (INOA) in a Chinese population. DESIGN: Case-control study. SETTING: Medical academy and hospital. PATIENT(S): Two hundred twenty-nine INOA patients and 236 fertile male controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): 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). RESULT(S): 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. CONCLUSION(S): 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. CI - Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved. FAU - Li, Zhongxiang AU - Li Z AD - Center for Reproductive Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang Province, People's Republic of China. Electronic address: zhongxiangli@gmail.com. FAU - Yu, Jianmin AU - Yu J FAU - Zhang, Tao AU - Zhang T FAU - Li, Hongchao AU - Li H