在囊性纤维化中肝病的遗传修饰剂
Jaclyn R Bartlett1, Kenneth J Friedman, Simon C Ling
1Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
JAMA
|September 10, 2009
概括
塞尔皮纳1Z等位基因是囊性纤维化 (CF) 患者严重肝病的重要危险因素. 携带这种等位基因的个体面临患这种并发症的风险增加了大约五倍.
科学领域:
- 遗传学 是一个遗传学.
- 肝病学 肝病学是一种肝病学.
- 肺部病理学 肺部病理学
背景情况:
- 囊性纤维化 (CF) 影响多个器官,其中一小部分患者患有严重的肝病和门性高血压.
- 识别影响CF并发症的遗传因素对于个性化医学至关重要.
研究的目的:
- 研究五个候选基因中的多态化与CF患者严重肝病的发展之间的关联.
- 具体研究的是α(1) -抗素 (SERPINA1),血管素转化酶 (ACE),谷氨S转移酶 (GSTP1),曼诺结合性莱克2 (MBL2) 和转化生长因子β1 (TGFB1).
主要方法:
- 这是一项两阶段的病例控制研究,涉及多个国际中心的CF患者,有或没有严重的肝病.
- 在候选基因中对九种多态基因的基因定型.
- 后勤回归分析以确定基因型与疾病状态之间的关联.
主要成果:
- 在最初和复制阶段,SERPINA1 Z等位基因与严重的肝病有很强的关联.
- 在TGFB1编码子10 CC基因型中,在初步研究中显示出关联,但在复制阶段没有.
- 综合分析证实了SERPINA1 Z等位基因与CF相关的肝病之间的显著关联 (OR,5.04;P = 1.5 x 10(-8)).
结论:
- 塞尔皮纳1Z等位基因是囊性纤维化中严重肝病的确诊危险因素.
- 携带SERPINA1 Z等位基因的CF患者患肝脏并发症的风险大大增加.
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