Yale Daily News
Alcohol enzymes differ across Asian groups
Original address: http://www.yaledailynews.com/articles/view/24328 [Back to the list]
Kenneth Kidd, professor of genetics, psychiatry and ecology and evolutionary biology, chuckles softly as he explains that the ¡°Asian flush¡± is actually rooted in science.
¡°We all have East Asian friends who turn bright red with alcohol,¡± Kidd said.
The reason for this ¡°flushing reaction,¡± he explained, is that many Asians carry variants of genes regulating alcohol metabolism that make them feel uncomfortable or even ill when drinking small amounts of alcohol. Because of environmental change, evolution in East Asian communities sometime over the past few thousand years selected for these genetic mutations, protecting those who carried them from alcoholism, Kidd said.
This much scientists have known for several decades. But now, new research at Kidd¡¯s lab suggests that, within East Asian communities, the prevalence of the genetic variant is associated with culture: Some linguistic groups, specifically the Hmong- and Altaic-speaking groups, carry it with higher frequency than other groups.
¡°What this finding does is highlight that something important in recent human history has affected the genetic composition of some, but not other, East Asian populations,¡± Kidd said.
The findings suggest something was slightly different in the environment of those populations throughout history, and that the genetic variant assisted survival in that environment. Hence, groups evolved divergently because of different environmental pressures.
Hui Li, lead author on the study, said there are at least seven different ethnic groups within East Asia ¡ª contrary to popular conceptions that ¡°all Asians are the same¡± ¡ª and that some are scattered across more than one country. The Altaic-speaking group, for instance, spans from Turkey to Japan, he said.
Kidd¡¯s team studies a variant of ADH1B, one of a set of related genes that code for alcohol dehydrogenases, enzymes that metabolize alcohol. The particular variant studied was found to be prevalent in as high as 90 percent of some populations. The mutation seems to ¡°protect¡± against alcoholism, since East Asian alcoholics lack it, Kidd explained.
While Kidd¡¯s lab has now shown that natural selection caused the genetic variant in the populations in which the allele is common, how or why that mutation came about is still far from clear, Li said.
Very recent migration events, at least, can be ruled out. Li said the ethnic groups that started out in one place but now live in another ¡ª such as Thai individuals originally from Canton, in China ¡ª show the allele frequency of those in their original environment.
The idea that the variant was selected for because it protected groups against alcoholism seems unlikely, Kidd said, since such a minor advantage would not produce such wide-scale selection.
One dominant hypothesis, he said, holds that a food toxin present in the diets of certain communities, but not others, made the gene advantageous.
The idea, Kidd said, is that the same variant that makes East Asians feel ill in response to acetylaldehyde ¡ª the compound created when alcohol is metabolized ¡ª may work to protect them against an alcoholic compound in a food common to their culture that would normally be toxic.
If this were true, it would explain why, as the study found, the variant¡¯s prevalence differed across linguistic groups, each of which tends to eat slightly different kinds of food, he added.
A competing hypothesis maintains that the variant may have helped protect against parasites without the ability to degrade acetylaldehyde, a toxic substance. The genetic mutation causes those who have it to convert ethanol to acetylaldehyde more rapidly than usual, increasing the levels of transient acetylaldehyde in their bodies, Kidd explained. This increased concentration could have killed some parasites in the immediate vicinity, reducing the chance of those individuals¡¯ infection, he said.
¡°The evidence for the selection is there. We¡¯re seeing the evidence today,¡± Andrew Pakstis, co-author on the study, said. ¡°But the selection event ¡ª whether something in the disease environment, or lifestyle or physical location, or migration pattern ¡ª is still unknown.¡±
Li said the Kidd lab is not in a position to put the pieces of the puzzle together, since the study would require extensive field research and an in-depth understanding of the environmental factors that East Asian groups have been exposed to across time.
Pakstetis said the selection event could have been very brief, or extended, but how long ago the event occurred is not known. In fact, Li said, the selection process may still be going on.
But Kidd said genetic factors alone may not explain the low prevalence of alcoholism among East Asian communities. Rather, much of the phenomenon may be traced to cultural norms, he said.
¡°If a large part of the people got sick after they ate one particular food or drank a particular drink, you would not find many social situations where that food was served,¡± Kidd said.
The next step, Li said, is to determine when the selection event occurred. Scientists will now work on dating the variant DNA and looking for samples of ancient DNA to try to pinpoint the exact date at which the mutation was incorporated into the genomes of the groups under study.