Refined geographic distribution of the oriental ALDH2* 504Lys (nee 487Lys) variant

Hui Li, Svetlana Borinskaya, Kimio Yoshimura, Nina Kal'ina, Andrey Marusin, Vadim A. Stepanov, Zhendong Qin, Shagufta Khaliq, Mi Young Lee, Yajun Yang, Aisha Mohyuddin, David Gurwitz, Syed Qasim Mehdi, Evgeny Rogaev, Li Jin, Nikolay K. Yankovsky, Judith R. Kidd, Kenneth K. Kidd

Research output: Contribution to journalArticlepeer-review

223 Citations (Scopus)


Summary: 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.

Original languageEnglish
Pages (from-to)335-345
Number of pages11
JournalAnnals of Human Genetics
Issue number3
Publication statusPublished - 2009


  • Alcohol associated
  • Aldehyde dehydrogenase 2
  • Allele frequency
  • East Asia
  • Esophageal cancer

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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