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THE GENETICS OF ALCOHOL which these variants occur in one par­ protection against alcohol-related birth METABOLISM: ROLE OF ticular group of Native Americans, the defects. (pp. 18–21) Southwest California Indians. The find­ AND ALDEHYDE ings suggest that it is unlikely that ALDH2, ADH1B, AND ADH1C DEHYDROGENASE VARIANTS Native Americans carry a genetic vari­ GENOTYPES IN ASIANS: A ant that predisposes them to . LITERATURE REVIEW lcohol is metabolized by several A Certain variants of ADH and ADLH pathways, the most common of revious studies have shown that the which involves two key enzymes— do have a protective affect against alco­ holism in some Native American peo­ Pprevalence of certain variations of alcohol dehydrogenase (ADH) and alde­ for the alcohol-metabolizing hyde dehydrogenase (ALDH). Genetic ple; however, these findings do not explain the high incidence of alcoholism enzymes alcohol dehydrogenase (ADH) differences in these enzymes may help and (ALDH) to explain why some groups of people in the tribes that were studied. (pp. 14–17) can vary across Asian ethnic groups and have higher or lower rates of alcohol- may cause some groups to have higher related problems. For example, certain rates of alcohol dependence than others. variations in the genes that produce HEALTH-RELATED EFFECTS OF GENETIC VARIATIONS OF For example, relatively high rates of alco­ ADH and ADH have been shown to hol dependence have been determined have a protective effect in that they lead ALCOHOL-METABOLIZING among Koreans and Korean Americans, to an increased production of acetalde­ ENZYMES IN AFRICAN whereas relatively low rates have been hyde, a toxic byproduct of alcohol AMERICANS metabolism that can cause adverse phys­ found in Chinese and Chinese ical reactions, such as facial flushing, he way alcohol is metabolized by the Americans. In this article, Drs. Mimy Y. nausea, and rapid heart beat. This arti­ Tbody not only influences drinking Eng, Susan E. Luczak, and Tamara L. cle by Dr. Howard J. Edenberg exam­ behavior but also may play a role in the Wall discuss the prevalence of three ines the role ADH and ALDH variants development of alcohol dependence and variants—ALDH2, ADH1B, and play in alcohol metabolism and the alcohol-induced organ damage. Two key ADH1C—among Asian ethnic groups. risk for alcoholism. This article also dis­ alcohol-metabolizing enzymes—alcohol (pp. 22–27) cusses the correlation between occur­ dehydrogenase (ADH) and aldehyde rence of these genes and alcoholism risk dehydrogenase (ALDH)—and their VARIATIONS IN ALCOHOL­ in various ethnic populations. (pp. variants have been shown to influence METABOLIZING ENZYMES IN PEOPLE OF EAST INDIAN 5–13) the risk of alcohol dependence because AND AFRICAN DESCENT they mediate the production of acetalde­ VARIATIONS IN ADH AND FROM TRINIDAD AND hyde, the toxic byproduct of alcohol TOBAGO ALDH IN SOUTHWEST metabolism that causes the adverse CALIFORNIA INDIANS effects of alcohol consumption. Previous n Trinidad and Tobago, differences studies have determined that the preva­ ative Americans and Alaskan Oin alcoholism rates exist among lence of certain variants of ADH and NNatives are five times more likely people of East Indian (Indo-Trinidadian) than other ethnicities in the United ALDH varies in different ethnic popu­ and African (Afro-Trinidadian) ancestry. States to die of alcohol-related causes. lations. In this article, Drs. Denise M. Researchers have investigated whether Native Americans are predisposed to Scott and Robert E. Taylor examine the these differences can be explained in part alcoholism because of differences in the prevalence and effects of genetic variants by variations in the genes that produce way they metabolize alcohol. In this arti­ of ADH and ALDH genes in African the alcohol-metabolizing enzymes alco­ cle, Dr. Cindy L. Ehlers examines stud­ Americans. For example, one of the hol dehydrogenase (ADH) 1B and 1C ies that test this hypothesis. Individuals ADH1B gene variants has been found and aldehyde dehydrogenase (ALDH) can be protected against or predisposed in up to one-fourth of the people of 1 and 2 and cytochrome P450 2E1 to alcoholism by variations in the African descent. This variant results in (CYP2E1). In this article by Ms. Shelley enzymes that metabolize alcohol (i.e., a higher rate of alcohol metabolism and Moore and Drs. L.K. Montane-Jaime, alcohol dehydrogenase [ADH] and alde­ has been associated with a reduced like­ Lucinda G. Carr, and Cindy L. Ehlers, hyde dehydrogenase [ALDH]). Dr. lihood of a family history of alcoholism, the authors discuss studies of ADH Ehlers examines the frequency with less positive response to alcohol, and and ALDH genetic differences in

Vol. 30, No. 1, 2007 3 IN THIS ISSUE

Trinidadians. These studies highlight the by Drs. Helmut K. Seitz and Peter EFFECTS OF PREGNANCY usefulness of evaluating risk and protec­ Becker examines the role of alcohol AND NUTRITIONAL STATUS tive factors associated with alcohol metabolism in alcohol-associated cancer ON ALCOHOL METABOLISM metabolism in diverse ethnic groups. development, focusing mainly on the (pp. 28–30) contribution of acetaldehyde and on etal Alcohol Spectrum Disorder genetic risk factors leading to increased F(FASD) is a constellation of physical, ALCOHOL METABOLISM AND acetaldehyde levels. (pp. 38–47) behavioral, and cognitive abnormalities CANCER RISK that can result when a fetus is exposed ROLE OF ALCOHOL to alcohol in utero. However, only a hronic alcohol consumption METABOLISM IN CHRONIC Cincreases the risk for cancer of the PANCREATITIS small percentage of children exposed to organs and tissues of the respiratory and alcohol during development display upper digestive tract, liver, colon, rectum, lcohol abuse is the major cause of symptoms of FASD, and the mecha­ and breast. Various factors contribute to Achronic inflammation of the pan­ nisms by which FASD develops are the development of alcohol-associated creas (i.e., pancreatitis). It has been unknown. In this article, Drs. Kartik cancer, including the effects of acetalde­ believed that alcoholic pancreatitis is a Shankar, Martin J.J. Ronis, and Thomas hyde, the toxic byproduct of alcohol chronic disease, but recent findings have M. Badger speculate that nutrition and metabolism. Alcohol dehydrogenase shown that it may be caused by frequent (ADH) and aldehyde dehydrogenase acute tissue death and inflammation. In alcohol exposure may interact to con­ (ALDH), which are encoded by multi­ this article, Drs. Alain Vonlaufen, tribute to the development of FASD. ple genes and exist in several variants, Jeremy S. Wilson, Romano C. Pirola, Because undernutrition can slow the are key enzymes involved in alcohol and and Minoti V. Apte, discuss the type of rate of alcohol metabolism, and expo­ acetaldehyde metabolism. Because cer­ pancreas cell that produces digestive sure to alcohol may contribute to under­ tain variants may result in elevated juices (i.e., acinar cell) and how alcohol nutrition, it is difficult to determine the acetaldehyde levels, the presence of these exerts toxic effects on these cells. In addi­ precise effects of these factors. However, variants may predispose individuals to tion, there now is sufficient evidence the researchers suggest that improving certain cancers. Moreover, highly reactive, that the pancreas has the capacity to maternal nutrition during pregnancy, oxygen-containing molecules (reactive metabolize alcohol via both oxidative oxygen species) that are generated dur­ and nonoxidative pathways. The result­ which minimizes fetal exposure to alco­ ing certain pathways of alcohol ing metabolites and their byproducts hol, might reduce the incidence of metabolism can damage the DNA and also exert a toxic effect on the pancreas. FASD among high-risk populations. induce tumor development. This article (pp. 48–54) (pp. 55–59)

4 Alcohol Research & Health