A number of chronic diseases, including cardiovascular disease, appear to have a multifactorial genetic risk component. Consequently, techniques are needed to facilitate evaluation of complex genetic risk factors in large cohorts. We have designed a prototype assay for genotyping a panel of 35 biallelic sites that represent variation within 15 genes from biochemical pathways implicated in the development and progression of cardiovascular disease. Each DNA sample is amplified using two multiplex polymerase chain reactions, and the alleles are genotyped simultaneously using an array of immobilized, sequence-specific oligonucleotide probes. This multilocus assay was applied to two types of cohorts. Population frequencies for the markers were estimated using 496 unrelated individuals from a family-based cohort, and the observed values were consistent with previous reports. Linkage disequilibrium between consecutive pairs of markers within theapoCIII, LPL, and ELAM genes was also estimated. A preliminary analysis of single and pairwise locus associations with severity of atherosclerosis was performed using a composite cohort of 142 individuals for whom quantitative angiography data were available; evaluation of the potentially interesting associations observed will require analysis of an independent and larger cohort. This assay format provides a research tool for studies of multilocus genetic risk factors in large cardiovascular disease cohorts, and for the subsequent development of diagnostic tests.

THE CONCLUSION of a recent meta-analysis¹ on drinking and mortality was that the results were "inconsistent with the belief that daily consumption of a few glasses of wine has salutary effects." To conclude whether wine may have salutary effects, its influence on all-cause mortality should be precisely evaluated. Recent prospective studies^2-6 observed that a moderate intake of alcohol was associated with a lower overall death rate. However, only 2 of these studies determined the respective role of the different alcohols. In Shanghai, China,⁵ the consumption of wine, mostly rice wine, was not more beneficial than that of beer or spirits. By contrast, in Denmark⁶ only the moderate intake of wine (grape wine) could lower mortality from cardiovascular and other causes. Grape wine appears to be the main alcoholic beverage that contains antioxidant phenolic substances, which are known to inhibit oxidation of low-density lipoprotein⁷ and affect platelet functions.⁸ Among these substances, resveratrol may even inhibit the 3 main stages of carcinogenesis.⁹

The effects of alcohol consumption on plasma concentrations of antioxidant vitamins (α-tocopherol and ascorbic acid), selenium, and markers of oxidative stress, especially malondialdehyde (MDA) and autoantibodies directed to MDA adducts to proteins (Ig-NH₂-MDA) were investigated in a large population of 417 supposedly healthy men who consumed only low or moderate amounts of alcohol as compared with 102 alcoholic patients without severe liver disease, who were studied both before and after 21 d of withdrawal treatment. Plasma concentrations of α-tocopherol, ascorbic acid, and selenium were lower in alcoholics than in men who drank low amounts of alcohol (P ≤ 0.001), whereas MDA and Ig-NH₂-MDA were higher (P ≤ 0.001). Plasma concentrations of α-tocopherol and selenium remained unchanged after the withdrawal period, whereas ascorbic acid (P ≤ 0.01), MDA, and Ig-NH₂-MDA concentrations decreased (P ≤ 0.001). Adjustment of data for circulating lipids and nutritional intake suggests a specific effect of alcohol on antioxidant vitamins, independent of nutritional status.