Variations in genes coding for metabolic enzymes cause a lesser tolerance for alcohol in Asian populations – with a nice side effect!

Alcohol from Asians, but better not for all Asians. Source

Intro

People of different regions are not only different in looks, but also carry differences in genes coding for functional pathways like the metabolic system. One of the more famous examples for these so-called “polymorphisms” are variations in genes coding for alcohol dehydrogenase and aldehyde dehydrogenase, two crucial enzymes required for the detoxification after alcohol consumption.

Read on to get a crash course in what polymorphisms are, how they can affect the metabolic inactivation of ethanol and what problems, but also advantages this brings for East-Asian populations.

Polymorphisms

From a genetic point of view, no human is equal (except for identical twins). Even as we all share 99.8% of our DNA, we don’t look, act and feel alike. Responsible for that fact are so-called polymorphisms (Greek: poly = many, morph = shape, form), defined as genetic variations that are non-pathogenic (=not causing an illness) and appear in at least 1% of the population. To date, more than 10 million polymorphisms have been described for humans and the average person differs in about 4 million genes.

As we know, genes are coding for proteins, and proteins carry out all the important functions of cells/organisms. So polymorphisms lead to the expression of slightly different proteins, which then effect different body features and functions. Some of them are visible, for example different eye, hair and skin color or body height, but some are hidden to the eye, affecting biochemical systems inside our organism. And that’s where my main topic of this week, the xenobiotic metabolism, enters the stage once again.

The metabolism of ethanol

Ethanol is metabolized via a two-step reaction including two enzymes. Source

Rarely a toxin can be described as "popular", but this one really is. I'm talking about ethanol, a.k.a. “the” alcohol, the probably most popular xenobiotic world-wide. As mentioned in my previous post, our body gets rid of ethanol by metabolizing it in the liver, first to acetaldehyde and in a second step to acetic acid, which can be excreted via the kidneys to our urine. To perform this two-step chemical reaction, it uses two enzymes. Alcohol dehydrogenase (ADH) catalyzes the first step, aldehyde dehydrogenase (ALDH) the second.

  Ever seen an Asian turn red after drinking alcohol? Chances are he is carrying the ALDH2 polymorphism. Source

The ALDH2 variation in East-Asian populations  

Of note, there are several known genetic variations in ADH and ALDH-related genes. Most of them have an insignificant effect, but some have serious consequences for their carriers. This especially applies to a polymorphism in the ALDH2 gene called “rs671”, which drastically reduces the work-rate of the ALDH. Therefore, if you are a carrier of this genetic variation and you drink too much alcohol, you will be unable to process the formed acetaldehyde fast enough, and the chemical will accumulate in your body, leading to the common symptoms of acetaldehyde poisoning, including hot red flushes and severe headache.

Very interestingly, the distribution of rs671 is concentrated in East Asia, as you can see on the map below. In China and Japan, almost 50% of the people carry at least one gene with this variation, while in Europe or Africa, it is almost non-existent. It is a mystery why evolution cursed Asians like that, but this is the reason why Eastern Asians – on average – don’t respond so well to alcohol consumption as compared to caucasians.

The global distribution of the rs671 polymorphism (green) in the ALDH2 gene. Source

Poor guys, you think? Ha, but there is an upside!

Several studies found carriers of rs671 to be much less likely to develop alcoholism with all the related health issues including liver cirrhosis and cancer. Which is logical: They don’t respond well to alcohol, so they drink less. And ultimately, they are healthier for that reason.

Conclusion  

So if your Asian friend doesn’t want to keep up with your drinking, have mercy! There might be a genetic reason. He will probably outlive you, so you might even consider to drink his/her beer to gain oblivion of that fact.

 

Sources: 

Review 1
Review 2
NIAAA
Wiki for cross-checking less sophisticated facts

Disclaimer: In my blog, I'm stating my honest opinion as a   researcher, not less and not more. Sometimes I make errors. Discuss and disagree with me - if you are bringing the better arguments, I might rethink.