Testing genetic susceptibility loci for alcoholic heart muscle disease

Background: Although many heavy alcohol users have subclinical alcoholic he art 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 ma y exist. In this work we examined whether common gene variants previously a ssociated with cardiac hypertrophy or altered alcohol metabolism could modi fy the effects of alcohol on the heart. Methods: We studied 700 middle-aged male victims of sudden death who underw ent a medicolegal autopsy. In addition to routine postmortem examination, t he weights and the cavity and wall dimensions of the left and right ventric le were measured. Coronary artery stenoses were deter-mined from a silicone rubber cast of the arteries. Alcohol consumption and cardiovascular risk f actors were assessed by a structured interview of the spouse. The following gene polymorphisms were determined by using polymerase chain reaction rest riction fragment length polymorphism and solid-phase minisequencing techniq ues: angiotensin converting enzyme I/D, angiotensin II type 1 receptor 1166 A/C, aldosterone synthase -344C/T, alcohol dehydrogenases 2 and 3, acetalde hyde 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 tota l heart weight and a larger right ventricle size with increasing daily drin king. 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 f actors determine the individual susceptibility to alcoholic heart muscle di sease.