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发表于 2004-3-25 00:54
5.1.2.ADH3基因多态性:用限制性内切酶SspⅠ消化ADH3基因第8外显子,发现ADH3位点存在野生型的ADH3*1和突变型ADH3*2(G1048A)两种等位基因,分别编码γ1和γ2两种亚单位,形成3种基因型,包括快代谢型ADH3*1/*1与慢代谢型ADH3*1/*2和ADH3*2/*2。ADH3*1在欧美白种人中的等位基因频率为50%-60%,在黑人中为85%。而在亚洲人中高达95%,存在着明显的种族差异。ADH3多态与饮酒方式有关,携带ADH3*2慢代谢等位基因的个体易产生酒精依赖,导致酒精中毒。Day等[34]的研究显示,ADH3*1的频率在对照组为55.1%,肝硬化组为62.7%,其差别无统计学意义(P>0.05)。最近Frenzer A等[35]报道ADH3*2/*2 及 ADH2*1/*1等位基因与酒精性肝硬化及酒精性胰腺炎相关。.
5.2.乙醛脱氢酶(ALDH)的多态性:
已发现ALDH有12种同工酶,常见的有4种,分别定位于不同的染色体的4 个基因编码。定位于12号染色体的ALDH2是线粒体ALDH的主要编码基因,ALDH2是乙醛的主要代谢酶,与60%以上的乙醛代谢有关,在ALDH2的第12外显子存在限制性内切酶MboⅡ的多态位点,从而形成野生型的ALDH2*1和突变型的ALDH2*2(G1510A)两种等位基因。基因型为ALDH2*1/*1者具有ALDH酶活性,而基因型为ALDH2*1/*2和ALDH2*2/*2者,因饮酒后可使乙醛氧化为乙酸延迟而被认为不具有ALDH酶的活性。在朝鲜人中ALDH2*1和ALDH2*2的频率分别为0.84和0.16。在日本人中,则分别为0.73和0.27,大约50%为无ALDH2活性的ALDH2*1/*2和ALDH2*2/*2基因型,而在白种人中ALDH2*2的频率很低[36]。在中国和日本的酗酒者中,ALDH2*2的频率明显低于非酗酒者,而在酗酒者中,ALDH2*1/*2可能是酒精性肝病的危险因素[37]。
六.结语:
基因多态性的研究是目前国内外学术界科研的热点。本文就与肝病有关的一些较常见的基因的多态性进行了总结,从中可窥出肝病与基因多态研究最新进展情况。基因芯片等新技术的出现,研究基因多态性的方法更加方便、简单。随着与肝病有关的基因新的多态性位点被发现,基因多态性与肝病相关性研究的更加深入广泛,论文也会越来越多。其目的在于通过对肝病相关基因多态性的研究,不仅可以从遗传学的角度在分子水平阐明肝病的发病机理,而且还可以为肝病的预防、判断预后及基因治疗提供理论依据和新思路。
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作者单位:430030 华中科技大学附属同济医院肝病研究所
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