rs189037, a functional variant in ATM gene promoter, is associated with idiopathic nonobstructive azoospermia
rs189037, a functional variant in ATM gene promoter, is associated with idiopathic nonobstructive azoospermia
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rs189037 是 ATM 基因启动子的功能变异，与特发性非梗阻性无精症相关
DOI：
10.1016/j.fertnstert.2013.07.1995
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发表时间：
2013-12-01
影响因子：
6.7
通讯作者：
Ni, Ya
中科院分区：
文献类型：
--
作者：
Li, Zhongxiang;Yu, Jianmin;Ni, Ya
目的：探讨atm基因启动子功能变异rs189037(G>；A)与中国人群特发性非梗阻性无精子症的关系。设计：病例对照研究。地点：医学院校和医院。患者(S)：229例非梗阻性无精子症患者和236例正常生育男性对照。干预(S)：无。主要结果衡量(S)：采用聚合酶链式反应限制性片段长度多态性进行基因分型，并经测序证实。计算危险基因型和等位基因的优势比(OR)和95%可信区间(95%CI)。结果：rs189037(G>；A)基因座的AA等位基因和A等位基因均与骨质疏松症的发病相关，其OR值分别为1.90(95%CI 1.214~3.007)和1.41(95%CI 1.112~1.775)。GA杂合子和GA+AA杂合子与INOA值无关，OR值分别为1.06(95%CI 0.761~1.472)和1.28(95%CI 0.954~1.708)。同时，分型分层分析显示，与GG组相比，AA组INOA患者的FSH水平较高，总T水平较低，睾丸体积较小。此外，生物信息学分析预测rs189037(G>；A)变异位于ATM启动子的保守区域，等位基因G向等位基因A的转变可能通过改变转录因子E2F1的DNA结合能力而导致ATM基因的差异表达。结论(S)：ATM基因启动子的rs189037(G>；A)变异可能通过影响E2F1的DNA结合能力和随后的ATM表达而导致中国人群INOA的风险增加。(C)2013年，由美国生殖医学学会提供。
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. (C) 2013 by American Society for Reproductive Medicine.