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Genotype frequencies of the Val384Asp missense mutation in the hMLH1 gene in patients with familial gastric cancer

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Author:: No author available

Journal Title:: WORLD CHINESE JOURNAL OF DIGESTOLOGY

Issue:: 16

DOI:: 10.3969/j.issn.1009-3079.2010.16.007

Key Word:: 家族性胃癌;hMLH1基因;Val384Asp

Abstract：目的:了解hMLH1基Val384Asp错义突变在家族性胃癌发病中的作用及Val384Asp可能的致病分子机制.方法:于江苏省淮安、泰兴及金坛三个肿瘤高发地区行现场调查,收集到100例2004年新发家族性或疑似家族性胃癌患者、180例健康人的外周血.应用PCR-DHPLC和DNA序列分析技术检测细胞的DNA,分析hMLH1基因的第12外显子,检测Val384Asp错义突变.生物信息学方法进行蛋白三维模型构建以及结构和功能学分析.结果:家族性/疑似家族性胃癌患者Val384Asp 检出率显著高于正常对照(OR=2.84,95%CI:1.07-7.81,P＜0.05).分组分析显示,Val384Asp 与胃癌相关癌前疾病有协同性(P＜0.01),并在发病年龄≥50岁的患者中显著分布(P＜0.05).此外,对胃癌家系进行患病风险的评估后,发现来自高风险家系的患者检出率较高(P＜0.05).蛋白三维模型显示,Val384Asp可以引起氢键的改变.可能影响hMLH1蛋白局部构象.功能学分析显示,降低蛋白功能和影响剪切调控是Val384Asp可能的致病机制.结论:中国家族性胃癌家系中的Val384Asp携带者可能有更高的胃癌发病风险.

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