Refined geographic distribution of the oriental ALDH2*504Lys (nee 487Lys) variant.
paper
Cited
Public
- Authors
- Li, Hui; Borinskaya, Svetlana; Yoshimura, Kimio; Kal'ina, Nina; Marusin, Andrey; Stepanov, Vadim A; Qin, Zhendong; Khaliq, Shagufta; Lee, Mi-Young; Yang, Yajun; Mohyuddin, Aisha; Gurwitz, David; Mehdi, Syed Qasim; Rogaev, Evgeny; Jin, Li; Yankovsky, Nikolay K; Kidd, Judith R; Kidd, Kenneth K
- Year
- 2009
- Journal
- Annals of human genetics
- PMID
- 19456322
- DOI
- 10.1111/j.1469-1809.2009.00517.x
- PMCID
- PMC2846302
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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| # | Section | Preview |
|---|---|---|
| 20 | Geographic Association with Esophageal Cancer Incidence | In Central Chinese populations, the heritability of esophageal cancer is estimated at around 49%β¦ |
| 21 | Geographic Association with Esophageal Cancer Incidence | In most areas of South China and Southeast Asia, the incidence of esophageal cancer is much lower⦠|
| 22 | Conclusion | In conclusion, we hypothesize that the oriental ALDH2*504Lys variant might have originated in the⦠|
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21β23 of 23
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