基因组甲基化和体重指数:全基因组分析
Katherine J Dick1, Christopher P Nelson1, Loukia Tsaprouni2
1Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Lancet (London, England)
|March 18, 2014
概括
成人肥胖与血液和脂肪组织中HIF3A基因位点的DNA甲基化增加有关. 这表明缺氧诱导因子通路可能在体重调节中起作用.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 人类遗传学 人类遗传学
- 代谢性疾病研究研究.
背景情况:
- 肥胖是一个复杂的健康问题,受遗传,环境和生活方式因素的影响.
- 虽然已知与体重指数 (BMI) 的遗传联系,但表观遗传因素仍然不太了解.
- 表观遗传修饰,如DNA甲基化,可能为肥胖的发展提供新的见解.
研究的目的:
- 对CpG位点的DNA甲基化进行基因组范围的分析,与BMI相关.
- 确定与BMI相关的特定甲基化位点,并在多个队列中验证这些发现.
- 探索已识别的甲基化位点,基因表达和遗传变异之间的关系.
主要方法:
- 在发现队列 (n=459) 中使用Infinium HumanMethylation450数组进行全基因组甲基化分析.
- 在两个独立的队列 (n=339和n=1789) 和脂肪和皮肤组织样本 (n=635和n=395) 中复制了重要的发现.
- 检查甲基化,BMI,基因表达和单核酸多态 (SNP) 之间的关联.
主要成果:
- 在HIF3A基因位点的三个探针中发现甲基化与BMI (q值≤0.05) 之间存在关联.
- 在HIF3A中,cg22891070的甲基化增加与发现和复制队伍中更高的BMI显著相关.
- 甲基化在cg22891070与脂肪组织中的BMI有关,与脂肪组织中的HIF3A基因表达相反相关.
结论:
- 欧洲血统成年人的BMI增加与血液和脂肪组织中的HIF3A位点的甲基化升高有关.
- 这些发现强调了缺氧诱导因子通路在身体对体重增加的反应中的潜在作用.
- 在HIF3A位点的表观遗传修饰代表了潜在的生物标志物和肥胖的治疗目标.
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