Workshop on Alcohol Use and Health Disparities 2002: a call to arms.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH) sponsored a "Workshop on Alcohol Use and Health Disparities 2002: A Call to Arms," on December 5, 2002, in Bethesda, Maryland, USA. This workshop was part of the NIAAA/NIH comprehensive strategic plan to reduce, and ultimately eliminate, health disparities. Eleven topics were addressed: (1). biomedical risk factors that may contribute to disparities in the toxic effects of alcohol; (2). alcohol and gene-environment interactions that affect the health of diverse groups; (3). alcohol pharmacogenetics in Mexican-Americans; (4). determinants of risk for alcoholism in minority populations; (5). consideration of population groups in linkage-disequilibrium studies to identify genes associated with alcohol dependence; (6). interaction between alcohol dependence and African-American ethnicity in disordered sleep, nocturnal cytokines, and immunity; (7). disparities of brain functional reserve capacity affecting brain morbidity related to substance abuse; (8). alcohol and pregnancy disparities; (9). role of alcohol in cancer risk disparities; (10). ethnic diversity in alcoholic cardiomyopathy; and (11). postmenopausal health disparities. On the basis of these presentations, seven conclusions emerged: (1). Genetic variations in alcohol-metabolizing enzymes exist in various populations. (2). These enzymes play a role in the variation in health effect outcomes seen in different populations, owing to alcohol consumption. (3). Differences between and among population groups can be critically important for the design and interpretation of studies in genetics. These include differences in expression of phenotype, in locus heterogeneity, in risk alleles, and in population structure. (4). Incidence rates for fetal alcohol syndrome and fetal alcohol spectrum disorders are greater in African-Americans and Native-Americans than in Caucasians. Genetic polymorphisms, nutrition, and other factors may account for these differences. (5). The highest mortality rate for cirrhosis has been found in white Hispanic men. (6). Mexican-Americans have a low frequency of the protective alleles ADH1B(*)2 and ALDH2(*)2 and a relatively high frequency of CYP2E1 c2, which is associated with early onset alcoholism. (7). The incidence rate for cancer is greater for African-Americans than for Caucasians, and part of the higher risk may be attributed to heavier drinking.

Role of iron in alcoholic liver disease: introduction and summary of the symposium.

The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on the "Role of Iron in Alcoholic Liver Disease" at Bethesda, Maryland, USA, October 2002. Alcoholic liver disease is a major cause of illness and death in the United States. Oxidative stress plays a key role in the pathogenesis of alcoholic liver disease. Iron can induce oxidative stress by catalyzing the conversion of superoxide and hydrogen peroxide to more potent oxidants such as hydroxyl radicals, which can cause tissue injury by initiating lipid peroxidation and causing oxidation of proteins and nucleic acids. Increasing evidence supports the suggestion that iron plays a significant role in the pathogenesis of alcoholic liver disease by exacerbating oxidative stress. Understanding the underlying mechanisms by which iron participates in the initiation and development of alcoholic liver disease may help design strategies for the treatment and prevention of the disease. For this symposium, nine speakers were invited to address the following issues: (1) iron intake from foods and dietary supplements; (2) hepatic iron overload in alcoholic liver disease; (3) iron-dependent activation of nuclear factor-kappa B (NF-kappaB) in Kupffer cells; (4) iron and cytochrome P450 2E1 (CYP2E1)-dependent oxidative stress and liver toxicity; (5) iron-induced oxidative stress in alcoholic hepatic fibrogenesis; (6) hemochromatosis and alcoholic liver disease; (7) iron as a co-morbid factor in nonhemochromatotic liver diseases; (8) iron and liver cancer; and (9) iron chelators and iron toxicity. On the basis of these presentations, it is concluded that heavy alcohol intake can result in increased accumulation of iron in the liver, in both hepatocytes and Kupffer cells. Iron-induced oxidative stress may promote the severity of alcoholic liver disease by (1) inducing NF-kappaB activation and subsequently increasing transcription of proinflammatory cytokines in Kupffer cells; (2) exacerbating CYP2E1-induced oxidative stress, especially in hepatocytes, through production of more toxic hydroxyl radicals; (3) stimulating hepatic stellate cells to produce excess amount of collagen and other matrix proteins that can lead to fibrosis; and (4) causing DNA damage and mutations that promote the development of liver cancer. Dietary iron supplements may further exacerbate the severity of alcoholic liver disease by increasing the magnitude of oxidative stress. We hope that the studies presented will stimulate further research in this exciting area.