Alcoholism, genetics, and race

Part-time GNXP houseboy / full-time mestizo failfuck "birch barlow" attributes his problems with alcohol and crack cocaine to "Anglo-Celtic" genes, while he raves about the quality genetics of small brown Asian women. It seems the self-proclaimed "cogelite" never bothered to actually check what genetic research suggests about relative group propensities for addictive behavior. So we're going to do it for him.

SNPedia lists several SNPs for which associations with Alcholism have been claimed, probably the most-studied of which is rs1800497:
rs1800497, a SNP also known as the TaqIA (or Taq1A) polymorphism of the dopamine D2 receptor DRD2 gene (even though it is actually located over 10,000bp downstream of the gene), gives rise to the DRD2*A1 allele. This allele (rs1800497(T)) is associated with a reduced number of dopamine binding sites in the brain [PMID 9672901], and has been postulated to play a role in alcoholism, smoking, and certain neuropsychiatric disorders.

The reduced number of dopamine binding sites may play a role in nicotine addiction by causing an "understimulated" state that can be relieved by smoking (and/or use of other drugs). [PMID 8873216]
The HapMap Phase III data indicates the following frequencies of the T/A (increased addiction risk) allele:
44% MEX (Mexican ancestry in Los Angeles, California)
44% CHB (Han Chinese in Beijing, China)
42% CHD (Chinese in Metroopolitan Denver, Colorado)
41% YRI (Yoruba in Ibadan, Nigeria)
40% ASW (African ancestry in Southwest USA)
40% JPT (Japanese in Tokyo, Japan)
28% GIH (Gujarati Indians in Houston, Texas)
21% CEU (Utah residents with Northern and Western European ancestry)
18% TSI (Toscans in Italy)

Not a good start for birch's imaginary mixed-race spawn. Let's look at another SNP:
rs1076560 is located in intron 6 of the dopamine receptor D2 gene.

In one study of Japanese males, rs1076560(A) alleles were 1.3 fold more associated with Alcoholism than the rs1076560(C) alleles. [PMID 17196743]

The DRD2 risk allele A was more prevalent in the alcoholic patients than in the healthy controls. These data identify rs1076560 as a potentially important variable in the development of alcoholism.
HapMap Phase III population frequencies for the A allele:
11% YRI (Yoruban)
12% TSI (Toscan)
14% ASW (Afram)
14% CEU (NW Euro)
27% GIH (Asian Indian)
36% MEX (Mexican)
40% JPT (Japanese)
45% CHB (Chinese)
46% CHD (Chinese)

Still not looking good. Next SNP:
The rs1799971(G) allele in exon 1 of the mu opiod receptor gene causes the normal amino acid at residue 40, asparagine, to be replaced by aspartic acid.

Carriers of at least one rs1799971(G) allele appear to have stronger cravings for alcohol than carriers of two rs1799971(A) alleles, and are thus hypothesized to be more at higher risk for alcoholism. [PMID 17207095]

Allele frequencies for rs1799971 (G):
4% ASW (Afram)
16% CEU (NW Euro)
18% TSI (Toscan)
20% MEX (Mexican)
33% CHB (Chinese)
42% GIH (Asian Indian)
46% JPT (Japanese)
47% CHD (Chinese)

By this point, birch should perhaps be thankful he's incapable of holding down a job long enough to buy that priced-to-sell Cambodian bride he has his eye on. Moving on:

Findings showed that SNP rs2232165 of the GHS-R1A gene was associated with heavy alcohol consumption (and therefore presumably alcohol dependence). SNP rs2948694 of the same gene as well as haplotypes of both the pro-ghrelin and the GHS-R1A genes were associated with an increased body mass in individuals consuming heavy amounts of alcohol.

Allele frequencies for rs2232165 (T):
8.3% YRI (Yoruban)
2.5% CEU (NW Euro)
0% CHB (Chinese)
0% JPT (Japanese)

Allele frequencies for rs2948694 (G):
33.8% JPT (Japanese)
32.4% CHB (Chinese)
9.6% YRI (Yoruban)
7.4% CEU (NW Euro)

But wait:
rs671 is a classic SNP, well known in a sense through the phenomena known as the "alcohol flush", also known as the "Asian Flush" or "Asian blush", in which certain individuals, often of Asian descent, have their face, neck and sometimes shoulders turn red after drinking alcohol.[PMID 6582480]

The rs671(A) allele of the ALDH2 gene is the culprit, in that it encodes a form of the aldehyde dehydrogenase 2 protein that is defective at metabolizing alcohol. This allele is known as the ALDH*2 form, and individuals possessing either one or two copies of it show alcohol-related sensitivity responses including facial flushing, and severe hangovers (and hence they are usually not regular drinkers). Perhaps not surprisingly they appear to suffer less from alcoholism and alcohol-related liver disease. [PMID 511165, PMID 16046871]
So much for "high executive function" saving Asians from the bottle. But only around a third of East Asians have genotypes associated with the flush reaction, and defective alcohol metabolism can't protect against opium (or cigarette) smoking. Unfortunately for birch:
"We have shown that Native Americans, who have a high rate of alcoholism, do not have these protective genes. The one that is particularly effective is a mutation of the gene for the enzyme aldehyde dehydrogenase, which plays a major role in metabolizing alcohol. The mutation is found very frequently in Chinese and Japanese populations but is less common among other Asian groups, including Koreans, the Malayo-Polynesian group, and others native to the Pacific Rim. "We've also looked at Euro-Americans, Native Americans, and Eskimos, and they don't have that gene mutation," says Li.
Amerindians also apparently have the world's highest frequencies of the DRD2 A1 allele, suggesting birch might be closer to the mark if he decided to blame his failure on his Amerindian ancestors.


Roland said...

From these results, would you say there is any conclusive evidence that any race/population is more likely to be addicted to dopamine releasing drugs (alcohol, opiates, cocaine etc).

If not would you say there is any perhaps inconclusive evidence that suggests certain races could be more predispositioned to addiction.

I am asking purely out of curiosity, so don't worry about your opinion being misused or misquoted.

n/a said...

I wouldn't make any strong pronouncements at this point. Much more research is required.

Anonymous said...

Other than in general those who we know have low impulse control.

Anonymous said...

Very nice information..but thats only half..yes the disease centers in the mind but the bodys innability to process acetone..produces the craving..whice completes the cycle..