Association of ALDH1 Promoter Polymorphisms with Alcohol-Related Phenotypes in Trinidad and Tobago * (Aldehyde Dehydrogenase) (Report‪)‬

GENETICALLY INFLUENCED METABOLIC factors have been implicated in the etiology of alcohol dependence. The major enzymes involved in alcohol metabolism, alcohol dehydrogenase (ADH) and mitochondrial aldehyde dehydrogenase (ALDH2), both exist as multiple isoenzymes that differ in their kinetic properties. Because the frequencies of these isoenzymes differ across ethnic groups, the genes that code for them have been considered candidate genes that are likely to contribute to variation in alcohol metabolism, response to alcohol, and individual vulnerability for developing alcohol dependence and alcohol-related disabilities (see Bosron et al., 1993; Crabb, 1995, 2004; Li, 1997, 2000). In approximately 40% of individuals of Far East Asian descent, a mutation in the gene that encodes for ALDH2 leads to a partially inactive form of the enzyme resulting in elevated acetaldehyde levels, an alcohol-induced flushing reaction, an increased level of response to alcohol, and lower rates of alcohol use and alcohol dependence (Higuchi et al., 1995; Luczak et al., 2002; Takeshita et al., 1994; Wall et al., 1992, 1993, 1999). Additionally, in one study, possession of an ALDH2*2 allele was associated with a decreased likelihood of regular drinking, binge drinking, and regular smoking (Wall et al., 2001). Cytosolic aldehyde dehydrogenase (ALDH1A1) is an important enzyme in the metabolism of acetaldehyde and in the synthesis of retinoic acid. The ALDH1A1 gene is expressed in the central nervous system as well as in other tissues and is known to be involved in both ethanol metabolism and cell differentiation (Stewart et al., 1996). ALDH1A1 has been implicated in several alcohol-related phenotypes, including alcohol-induced flushing, sensitivity to alcohol, and alcohol-use disorders (Spence et al., 2003; Ward et al., 1994; Yoshida et al., 1989). However, definitive data linking polymorphisms in this enzyme to several alcohol-related phenotypes are still emerging. Two polymorphisms (ALDH1A1*2 and ALDH1A1*3) in the promoter region of ALDH1A1 have recently been identified in a small sampling of Asian, Caucasian, and African American individuals. ALDH1A1*2 was observed at frequencies of 0.035, 0.023, 0.023, and 0.012 in Asian, Caucasian, Jewish, and African American individuals, respectively. ALDH1A1*3 was observed in African American individuals only, at a frequency of .029. Moreover, the ALDH1A1*3 allele was found in higher frequency in African American alcohol dependents compared with controls, suggesting it may enhance the risk for alcohol dependence in that population (Spence et al., 2003).