A functional polymorphism in the DNA methyltransferase-3A promoter modifies the susceptibility in gastric cancer but not in esophageal carcinoma.
A functional polymorphism in the DNA methyltransferase-3A promoter modifies the susceptibility in gastric cancer but not in esophageal carcinoma.
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DNA甲基转移酶3A启动子的功能多态性改变了胃癌的易感性，但不改变食管癌的易感性
DOI：
10.1186/1741-7015-8-12
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发表时间：
2010-02-03
期刊：
影响因子：
9.3
通讯作者：
Xie W
中科院分区：
文献类型：
--
作者：
Fan H;Liu D;Qiu X;Qiao F;Wu Q;Su X;Zhang F;Song Y;Zhao Z;Xie W
背景DNA甲基转移酶（DNMT）-3A在胚胎发育过程中起重要作用，在肿瘤发生过程中异常甲基化的产生也起重要作用。本研究旨在探讨DNMT 3A启动子基因多态性对其转录活性的影响，以及DNMT 3A基因多态性与中国人群胃癌和食管癌易感性的关系。G在DNMT 3A启动子区域中的表达，并使用荧光素酶测定评估其对活性的影响。采用聚合酶链反应/限制性片段长度多态性（PCR-RFLP/RFLP）方法检测DNMT 3A基因-448A>G多态性，并通过测序进行验证。检测208例胃癌患者和346例年龄、性别相匹配的健康对照者的-448A>G多态性分布。同时检测了96例食管癌患者和241例健康对照者的-448A>G多态性分布。结果在启动子检测中，携带-448A等位基因的启动子活性显著高于携带-448G等位基因的启动子活性（> 2倍）（P< 0.001）。GC患者和对照组中-448A等位基因频率分别为32.9%和19.9%。总的来说，我们发现，与GG携带者相比，DNMT 3A-448 AA纯合子具有> 6倍的GC风险增加。分层分析表明，AA纯合子在年龄范围≤ 60岁的GC个体亚组中具有更大的风险。然而，与携带-448GG基因型的个体相比，携带-448AG和-448AA的个体与EC的风险增加无统计学意义。结论DNMT 3A-448 A>G多态性是一种新的功能性SNP，有助于其对GC的遗传易感性。-448A>G可作为预测个体对GC易感性的分层指标，尤其是在≤ 60岁的个体亚组中。然而，-448A>G在EC中的相对分布不能作为预测个体对EC易感性的指标。
BackgroundDNA-methyltransferase (DNMT)-3A plays an important role in the development of embryogenesis and the generation of aberrant methylation in carcinogenesis. The aim of this study was to investigate the role of a DNMT3A promoter genetic variant on its transcriptional activity and to evaluate the association between DNMT3A gene polymorphism and the susceptibility to gastric cancer (GC) and oesophagus carcinoma (EC) in the Chinese population.MethodsWe selected one of the single nucleotide polymorphisms (SNPs) -448A>G in the DNMT3A promoter region and evaluated its effect on activity using a luciferase assay. -448A>G polymorphisms of DNMT3A were determined by polymerase chain reaction/restriction fragment length polymorphism and confirmed by sequencing. The distribution of -448A>G polymorphisms was detected in 208 GC patients and 346 healthy controls matched for age and gender. The distribution of -448A>G polymorphisms was also detected in 96 EC patients and matched 241 healthy controls. The association of -448A>G polymorphisms of DNMT3A and the risk of GC and EC was evaluated by stratified analysis according to the patient's age and gender.ResultsIn a promoter assay, carriage of the -448 A allele showed a significantly higher promoter activity (> two fold) compared with the -448G allele (P< 0.001). The allele frequency of -448A among GC patients and controls was 32.9% versus 19.9%, respectively. Overall, we found that, compared with GG carriers, the DNMT3A -448AA homozygotes has a > six fold increased risk of GC. Stratification analysis showed that AA homozygotes have a more profound risk in the subgroups of individuals at the age range ≤ 60 years in GC. However, individuals with -448AG and -448AA were not statistically significantly associated with an increased risk of EC compared with those carried the -448GG genotype.ConclusionsThe DNMT3A -448A>G polymorphism is a novel functional SNP and contributes to its genetic susceptibility to GC. -448A>G can be used as a stratification marker to predict an individual's susceptibility to GC, especially in the subgroups of individuals at the age range ≤ 60 years. However, the relative distribution of -448A>G in EC can not be used as a prediction marker in order to evaluate an individual's susceptibility to EC.
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影响因子：
2.4
作者：
Long, Chaozhong;Yin, Bangliang;Yuan, Yunchang
通讯作者：
Yuan, Yunchang
影响因子：
6.4
作者：
Park, Hannah Lui;Kim, Myoung Sook;Sidransky, David
通讯作者：
Sidransky, David
影响因子：
10.4
作者：
Benbrahim-Tallaa L;Waterland RA;Dill AL;Webber MM;Waalkes MP
通讯作者：
Waalkes MP
DOI：
10.1016/j.bbrc.2009.07.093
发表时间：
2009-09-25
影响因子：
3.1
作者：
Deng, Tao;Kuang, Ying;Fei, Jian
通讯作者：
Fei, Jian
影响因子：
8
作者：
Lee, S. H.;Kim, J.;Lee, Y. M.
通讯作者：
Lee, Y. M.