Genetic modification of the effect of alcohol consumption on CHD

Abstract

The deleterious health effects of high alcohol consumption are numerous and well recognized; however, the effect of moderate alcohol consumption on overall health continues to be a debated issue. Among the more prevalent diseases in Westernized countries, epidemiological research suggests that alcohol in moderation substantially reduces the risk of CHD, while it modestly increases the risk for certain cancers, such as breast and colon cancer. Despite the overwhelming data supporting the beneficial effect of moderate alcohol consumption on the cardiovascular system, some researchers are not convinced. Sceptics argue that the reduction in risk is attributed to a favourable lifestyle factor associated with moderate alcohol consumption, or that it may be attributed to constituents of alcoholic beverages other than ethanol, such as the antioxidants in the grapes. In order to promote overall health for the general public, it is necessary to elucidate these issues. One approach is to study population differences in alcohol metabolic efficiency, which is likely to contribute to an individual's susceptibility to alcohol-associated diseases. Among the population there is substantial variability in the efficiency to metabolize alcohol. Genetic variation among the alcohol-metabolizing genes is known to produce isoenzymes with distinct kinetic properties. Studying genetic differences that potentially influence disease susceptibility among populations may provide insight into the mechanism(s) for the relationship between risk factor and disease, such as alcohol and CHD.

Alcohol use and fasting glucose in a developing southern Chinese population: the Guangzhou Biobank Cohort Study

“…Raised fasting blood glucose is a risk factor for diabetes, so we examined the association of alcohol use with fasting blood glucose in an understudied population, that is, older southern Chinese, with a potentially different social patterning of alcohol use. As a check for residual confounding and social desirability bias, we also verified that alcohol use had the effects on blood pressure and high-density lipoprotein (HDL) cholesterol that would be expected from randomised controlled trials and Mendelian randomisation studies 12 – 15…”

“…In East Asians alleles of the genes for faster alcohol processing (ADH2) and for slower metabolising of the first metabolite of alcohol, that is, acetaldehyde (ALDH2*2), are more common than in Caucasians 15. These alleles or other linked genes could specifically modify the action of alcohol so as to increase fasting blood sugar.…”

“…To assess content and predictive validity of our choice of exposure variable, three validation outcomes were considered. These were systolic blood pressure, diastolic blood pressure and HDL-cholesterol because trials, randomised controlled trials and Mendelian randomisation studies have all indicated that alcohol use is monotonically associated with higher blood pressure12 – 14 and higher HDL-cholesterol 15…”

Relationship of Alcohol Consumption and Type of Alcoholic Beverage Consumed With Plasma Lipid Levels: Differences Between Whites and African Americans of the ARIC Study

“…1). These finding are intriguing in light of the fact that the mechanism(s) by which alcohol affects lipid measures remains largely unknown (13,46,47). The differences observed in whites and African Americans with respect to the effects of alcohol intake on lipid measures (never drinkers have different levels; heavy drinkers have similar levels) could potentially be explained by genetic differences and thus warrant further study.…”

Alcohol Use, Vascular Disease, and Lipid-Lowering Drugs

“…An interesting aspect is that of population differences in Alc metabolic efficiency, which is likely to contribute to an individual's susceptibility to Alc-related diseases. Studying genetic differences that potentially influence disease susceptibility among populations may provide insight into the mechanism(s) for the relationship between risk factor and disease, such as Alc and CHD (Hines, 2004).…”