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

Capsule:
Our case–control study, involving 229 idiopathic nonobstructive azoospermia (INOA) patients and 236 fertile male controls, indicates that rs189037(G>A) in ATM gene increases INOA risk, possibly through affecting ATM expression.

Authors:
Zhongxiang Li, M.D., Jianmin Yu, M.Sc., Tao Zhang, Ph.D., Hongchao Li, M.Sc., Ya Ni, M.Sc.

Volume 100, Issue 6, Pages 1536-1541.e1, December 2013

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.

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.

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