Testing genetic susceptibility loci for alcoholic heart muscle disease.
BACKGROUND
Although many heavy alcohol users have subclinical alcoholic heart muscle disease, only a very few develop severe dilated cardiomyopathy. Therefore, and because cardiac abnormalities correlate only weakly with the duration or quantity of drinking, individual susceptibility differences may exist. In this work we examined whether common gene variants previously associated with cardiac hypertrophy or altered alcohol metabolism could modify the effects of alcohol on the heart.


METHODS
We studied 700 middle-aged male victims of sudden death who underwent a medicolegal autopsy. In addition to routine postmortem examination, the weights and the cavity and wall dimensions of the left and right ventricle were measured. Coronary artery stenoses were determined from a silicone rubber cast of the arteries. Alcohol consumption and cardiovascular risk factors were assessed by a structured interview of the spouse. The following gene polymorphisms were determined by using polymerase chain reaction restriction fragment length polymorphism and solid-phase minisequencing techniques: angiotensin converting enzyme I/D, angiotensin II type 1 receptor 1166A/C, aldosterone synthase -344C/T, alcohol dehydrogenases 2 and 3, acetaldehyde dehydrogenase 2, and cytochrome P-450 2E1 DraI, PstI, RsaI, and MspI.


RESULTS
The most consistent effects of alcohol (p < 0.05) were a higher total heart weight and a larger right ventricle size with increasing daily drinking. However, these and other effects of alcohol were statistically fully independent of the studied genotypes.


CONCLUSIONS
The gene polymorphisms selected for and analyzed in our study are unlikely to modify the effects of alcohol on the heart. Other unknown factors determine the individual susceptibility to alcoholic heart muscle disease.
Kajander
O A
OA
Medical School, University of Tampere, Finland.
Kupari
M
M
Perola
M
M
Pajarinen
J
J
Savolainen
V
V
Penttilä
A
A
Karhunen
P J
PJ
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000150:complications*; D000809:Angiotensins / Q000235:genetics; D002874:Chromosome Mapping; D000431:Ethanol / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006331:Heart Diseases / Q000209:etiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics
D000809:Angiotensins; D000431:Ethanol