Refined geographic distribution of the oriental ALDH2*504Lys (nee 487Lys) variant.
Refined geographic distribution of the oriental ALDH2*504Lys (nee 487Lys) variant.
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DOI：
10.1111/j.1469-1809.2009.00517.x
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发表时间：
2009-05
影响因子：
1.9
通讯作者：
Kidd KK
中科院分区：
文献类型：
--
作者：
Li H;Borinskaya S;Yoshimura K;Kal'ina N;Marusin A;Stepanov VA;Qin Z;Khaliq S;Lee MY;Yang Y;Mohyuddin A;Gurwitz D;Mehdi SQ;Rogaev E;Jin L;Yankovsky NK;Kidd JR;Kidd KK
线粒体醛脱氢酶（ALDH 2）是人体酒精代谢中最重要的酶之一。东方ALDH 2 * 504 Lys变体作为显性阴性发挥功能，大大降低杂合子中的活性并消除纯合子中的活性。该等位基因与酒精性肝病、迟发性阿尔茨海默病、结直肠癌和食管癌等严重疾病相关，并且最为人所知的是防止酒精中毒。已经有数百篇不同语言的论文发表在这个变体上，提供了许多不同人群的等位基因频率数据。为了开发高度精确的ALDH2*504Lys全球地理分布，我们从86个群体样本中收集了4，091个个体的新数据，并从366个群体样本中收集了80，691个个体的已发表数据。该等位基因在除东亚以外的世界各地基本上不存在。ALDH2*504Lys等位基因在中国东南部的频率最高，在中国、日本、韩国、蒙古和中南半岛的大部分地区都有分布，从中国东南部开始频率呈放射状逐渐下降。由于中国南方土著人群的ALDH2*504Lys基因频率远低于中国南方汉族人群，因此我们认为，ALDH2*504Lys基因在中国汉族人群中传播至东亚地区时是由汉族人群携带的。食管癌在东亚发病率最高，可能与ALDH 2 * 504 Lys相关，因为摄入乙醇浓度最高的组织中乙醛增加的毒性作用。虽然食管癌和ALDH 2 * 504 Lys的分布并不精确相关，但这并不能反驳这一假设。总的来说，ALDH 2 * 504 Lys和疾病的精细尺度地理分布的研究可能有助于理解基因，疾病，环境和文化之间的多重关系。
Mitochondrial aldehyde dehydrogenase (ALDH2) is one of the most important enzymes in human alcohol metabolism. The oriental ALDH2*504Lys variant functions as a dominant negative greatly reducing activity in heterozygotes and abolishing activity in homozygotes. This allele is associated with serious disorders such as alcohol liver disease, late onset Alzheimer disease, colorectal cancer, and esophageal cancer, and is best known for protection against alcoholism. Many hundreds of papers in various languages have been published on this variant, providing allele frequency data for many different populations. To develop a highly refined global geographic distribution of ALDH2*504Lys, we have collected new data on 4,091 individuals from 86 population samples and assembled published data on a total of 80,691 individuals from 366 population samples. The allele is essentially absent in all parts of the world except East Asia. The ALDH2*504Lys allele has its highest frequency in Southeast China, and occurs in most areas of China, Japan, Korea, Mongolia, and Indochina with frequencies gradually declining radially from Southeast China. As the indigenous populations in South China have much lower frequencies than the southern Han migrants from Central China, we conclude that ALDH2*504Lys was carried by Han Chinese as they spread throughout East Asia. Esophageal cancer, with its highest incidence in East Asia, may be associated with ALDH2*504Lys because of a toxic effect of increased acetaldehyde in the tissue where ingested ethanol has its highest concentration. While the distributions of esophageal cancer and ALDH2*504Lys do not precisely correlate, that does not disprove the hypothesis. In general the study of fine scale geographic distributions of ALDH2*504Lys and diseases may help in understanding the multiple relationships among genes, diseases, environments, and cultures.
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影响因子：
6.8
作者：
Li, Dong-Ping;Dandara, Collet;Parker, M. Iqbal
通讯作者：
Parker, M. Iqbal
影响因子：
30.8
作者：
Hashibe, Mia;Mckay, James D.;Brennan, Paul
通讯作者：
Brennan, Paul
影响因子：
4.8
作者：
Larson, HN;Weiner, H;Hurley, TD
通讯作者：
Hurley, TD
DOI：
10.1126/science.1158554
发表时间：
2008-09-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen CH;Budas GR;Churchill EN;Disatnik MH;Hurley TD;Mochly-Rosen D
通讯作者：
Mochly-Rosen D
影响因子：
2.9
作者：
Fan, Yunhua;Yuan, Jian-Min;Yu, Mimi C.
通讯作者：
Yu, Mimi C.