Subjective response to alcohol and ADH polymorphisms in a select sample of young adult male East Indians and Africans in Trinidad and Tobago.

OBJECTIVE: Level of response to alcohol has been associated with risk of alcohol dependence in a number of ethnic groups. In the present study, subjective and objective responses to alcohol were evaluated in Indo-Trinidadians (Indo-T) and Afro-Trinidadians (Afro-T). Associations of alcohol dehydrogenase polymorphisms with response to alcohol, using the Subjective High Assessment Scale (SHAS), and breath alcohol concentrations (BrAC) were tested. METHOD: Regular male drinkers without alcohol dependence (n = 112) ages 18-25 years participated in alcohol challenge sessions consisting of placebo and two doses of alcohol (target BrAC: 0 g/dl for placebo, .04 g/dl low dose, and .08 g/dl high dose) and genotyped for variants in ADH1B*3 and ADH1C*2. RESULTS: Indo-T had significantly higher BrAC, pulse rates, and cortisol levels when compared with Afro-T but did not have significantly higher SHAS values. Higher responses on the SHAS items muddle/confused and nauseated were significantly associated with the presence of at least one ADH1B*3 allele following the high dose of alcohol in Afro-T. Indo-T with at least one ADH1C*2 allele displayed significantly different Drug × Time interactions for the SHAS item effects of alcohol at the low dose and for the SHAS items clumsy, muddle/confused, effects of alcohol, floating, drunk, and total at the high dose from Indo-T with two ADH1C*1 alleles. CONCLUSIONS: This is the first study that has investigated individual sensitivity to alcohol in a Caribbean population and in people of East Indian descent. Indo-T with at least one ADH1C*2 allele may be at higher risk for heavy drinking by feeling less of the effects of alcohol, including nausea. In Afro-T, having at least one ADH1B*3 allele appears to exert a protective effect by enhancing the unpleasant effects of alcohol, such as nausea and confusion.

The clinical course of alcoholism in Trinidad and Tobago.

OBJECTIVE: The clinical course of alcoholism has been described as a series of distinct, alcohol-related life events that occur in an orderly sequence. However, whether that sequence differs, depending on ethnicity and country of origin, is less clear. The purposes of this study were to investigate the sequence and progression of alcohol-related life events in individuals of East Indian (Indo) and African (Afro) heritage on the islands of Trinidad and Tobago, and compare those results with data reported previously by the Collaborative study for the Genetics of Alcoholism (COGA). METHOD: Participants who were alcohol dependent (based on Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria) and of Afro-Trinidadian and Tobagonian ancestry or Indo-Trinidadian ancestry were recruited from inpatient treatment facilities. A total of 148 alcohol-dependent men and women completed the Semi-Structured Assessment of the Genetics of Alcoholism, which assessed the physical, psychological, and social manifestations of alcohol dependence and other psychiatric disorders. RESULTS: A high degree of similarity in the sequence of alcohol-related life events was found between Indo-Trinidadian, Afro-Trinidadian and Tobagonian, and COGA participants. However, Trinidadian and Tobagonian alcoholics were more likely to endorse severe alcohol drinking in the form of binges (2 or more days of intoxication), blackouts, withdrawal, and medical consequences; however, they were less likely to endorse aggressive acts associated with drinking. Progression to alcohol dependence was significantly slower in Trinidadian and Tobagonian alcoholics than in the U.S. population of alcoholics, but severe alcohol symptoms were more commonly endorsed in Trinidadian and Tobagonians.

The clinical course of alcoholism in Trinidad and Tobago.

OBJECTIVE: The clinical course of alcoholism has been described as a series of distinct, alcohol-related life events that occur in an orderly sequence. However, whether that sequence differs, depending on ethnicity and country of origin, is less clear. The purposes of this study were to investigate the sequence and progression of alcohol-related life events in individuals of East Indian (Indo) and African (Afro) heritage on the islands of Trinidad and Tobago, and compare those results with data reported previously by the Collaborative study for the Genetics of Alcoholism (COGA). METHOD: Participants who were alcohol dependent (based on Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria) and of Afro-Trinidadian and Tobagonian ancestry or Indo-Trinidadian ancestry were recruited from inpatient treatment facilities. A total of 148 alcohol-dependent men and women completed the Semi-Structured Assessment of the Genetics of Alcoholism, which assessed the physical, psychological, and social manifestations of alcohol dependence and other psychiatric disorders. RESULTS: A high degree of similarity in the sequence of alcohol-related life events was found between Indo-Trinidadian, Afro-Trinidadian and Tobagonian, and COGA participants. However, Trinidadian and Tobagonian alcoholics were more likely to endorse severe alcohol drinking in the form of binges (2 or more days of intoxication), blackouts, withdrawal, and medical consequences; however, they were less likely to endorse aggressive acts associated with drinking. Progression to alcohol dependence was significantly slower in Trinidadian and Tobagonian alcoholics than in the U.S. population of alcoholics, but severe alcohol symptoms were more commonly endorsed in Trinidadian and Tobagonians. CONCLUSIONS: Identifying ethnic and country of origin differences in the clinical course of alcohol dependence may assist in the development of culturally sensitive intervention and prevention programs.

Association of ALDH1 promoter polymorphisms with alcohol-related phenotypes in Trinidad and Tobago.

OBJECTIVE: Two polymorphisms in the promoter region of the gene encoding cytosolic aldehyde dehydrogenase (ALDH1A1), ALDH1A1*2 and ALDH1A1*3, have recently been identified. The present study sought to determine whether an association exists between ALDH1A1 genotypes, alcohol dependence, drinking history, and liver function tests in the two major ethnic groups of Trinidad and Tobago (TT). METHOD: The participants in this study were 137 alcohol dependents of either East Indian ancestry (Indo-TT) or African ancestry (Afro-TT) and 108 controls matched by age, gender, and ethnicity. A structured interview was used to gather information on demographics, psychiatric diagnoses, and personal drinking and drug use. A blood sample was obtained from each participant, and leukocyte DNA was extracted and used to genotype for the presence of the ALDH1A1 promoter polymorphisms. Serum levels of hepatic enzymes, as well as presence of HIV, hepatitis B surface antigen, and antihepatitis C virus antibody, were also determined. RESULTS: Twenty-four participants (10%) possessed the ALDH1A1*1/*2 genotype (frequency = .05), 4 were Afro-TT (2 alcohol dependents, 2 controls), and 20 were Indo-TT (18 alcohol dependents, 2 controls). Two participants (1 Indo-TT alcohol dependent, 1 Afro-TT alcohol dependent) had the ALDH1A1*2/*2 genotype. Four participants possessed ALDH1A1*3, all of whom were Afro-TT controls. Indo-TT participants with at least one ALDH1A1*2 allele were more likely to have a lifetime diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, alcohol dependence (p < .002). Indo-TT participants with ALDH1A1*2 also reported significantly higher levels of current alcohol consumption (p < .05). The small number of Afro-TT participants with atypical polymorphisms limits any conclusions on the possible impact on alcohol dependence in that population. CONCLUSIONS: Results from this study suggest that ALDH1A1*2 may be associated with increased risk for the development of alcohol dependence in Indo-Trinidadians.

Association of the ADHIB*3 allele with alcohol-related phenotypes in Trinidad.

BACKGROUND: Two of the class I alcohol dehydrogenase (ADH) genes located on chromosome 4 (ADH1B and ADH1C) encode for multiple isozymes that differ in their kinetic properties. At the ADH1B locus, 3 polymorphisms are present (ADH1B(*)1, ADH1B(*)2, ADH1B(*)3). ADH1B(*)2 (found mostly in individuals of East Asian and Jewish descent) and ADH1B(*)3 (found mostly in individuals of African decent) alleles encode for a more active enzyme variants than ADH1B(*)1 and the presence of these alleles has been associated with protection from alcohol dependence. The relationship between these alleles and alcohol-associated phenotypes has not been previously investigated in individuals living in the Caribbean. METHODS: One hundred thirty-three alcohol-dependent individuals of either East Indian or African ancestry and 98 controls matched by age, sex, education, and ethnicity participated in the study. A structured interview [the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA)] was used to gather information on demographics, psychiatric diagnoses, personal drinking, and drug use history. Leukocyte DNA extracted from a blood sample obtained from each participant was genotyped at the ADH1B locus. Serum levels of the liver enzymes alanine and aspartate aminotransferase (ALT, AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) as well as the presence of HIV, hepatitis B surface antigen, and antihepatitis C virus antibody were also assayed. The specific aim of the study was to investigate the associations between ADH1B alleles and alcohol dependence, drinking history, and liver function in individuals from the 2 major ethnic groups of Trinidad (individuals of African and East Indian ancestry). RESULTS: Twenty-eight of the Afro-Trinidadian (Afro-TT) participants (41%) and 1 Indo-Trinidadian (Indo-TT) (>1%) had at least 1 ADH1B(*)3 allele and 3 Afro-TT were homozygous for the allele. African participants with at least 1 ADH1B(*)3 allele were found to be significantly less likely to be alcohol dependent (p<0.018), and to have lower alcohol consumption levels (p<0.05). Among those participants who were alcohol dependent, ADH1B(*)3 was associated with significantly higher levels of ALT (p<0.05). CONCLUSIONS: This study suggests, in this sample of Trinidadians, that the ADH1B(*)3 allele is associated with protection from the development of alcoholism but is also associated with enhanced risk for elevated serum ALT levels in those individuals who do become alcohol dependent.

ADH1C*2 allele is associated with alcohol dependence and elevated liver enzymes in Trinidad and Tobago.

Variants in alcohol dehydrogenase (ADH) genes differ between ethnic groups and have, in some studies, been found to be associated with alcohol dependence and alcoholic liver disease. This study sought to determine whether an association exists between ADH (ADH1C previously ADH3, ADH1B*2 previously ADH2*2) genotypes, alcohol dependence, drinking history, and liver function tests in the two major ethnic groups of Trinidad and Tobago (TT). One hundred and forty-five alcohol-dependent individuals of both East Indian (Indo-TT) and African (Afro-TT) ancestry, and 108 controls matched by age, sex, and education participated in the study. Serum levels of alanine and aspartate aminotransferase (ALT, AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT) as well as presence of HIV, hepatitis B surface antigen, and anti-hepatitis C virus antibody were determined. There was a significant difference in the distribution of ADH1C allele polymorphisms between the ethnic groups (P<.0001). Forty-three percent of the Indo-TT were found to have one ADH1C*2 allele and 5% were homozygous, whereas, only 23% of Afro-TT had one allele and one was homozygous. Only three individuals had an ADH1B*2 allele (one Indo-TT alcohol dependent, two Indo-TT controls). The ADH1C*2 allele was significantly associated with alcohol dependence overall and within Indo-TT ancestry, however, it was not associated with current or heaviest alcohol consumption levels. Individuals with at least one ADH1C*2 allele also had significantly elevated levels of ALP (P<.02) and GGT (P<.02) as compared to individuals homozygous for ADH1C*. Additionally, GGT levels were also found to be elevated (P<.02) within Indo-TT alcohol dependents with at least one ADH1C*2 allele but not within the Afro-TT alcohol dependents with that allele. A linear regression that included alcohol dependence and levels of alcohol consumption confirmed that levels of serum GGT were significantly associated with the ADH1C*2 genotype. These results suggest that ADH1C polymorphisms are associated with alcohol dependence and alcohol associated elevations of liver enzymes in a population with a low frequency of ADH1B2 alleles.