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.

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.

Association of the ADH2*3 allele with greater alcohol expectancies in African-American young adults.

OBJECTIVE: A polymorphism at the alcohol dehydrogenase (ADH) gene locus, ADH2*3, exhibits markedly greater capacity and maximal velocity for ethanol, and has been reported to occur exclusively in African Americans and some tribes of Native Americans. While it appears that this allele may produce protection from alcohol-induced morbidity, the mechanism by which it does so remains unknown. METHOD: This study examined the association between expectations of the effects of alcohol and the presence of the ADH2*3 allele in 66 African-American young adults (18-25 years old). A structured interview, alcohol-related expectancies and a blood sample were obtained from each participant. RESULTS: A positive association between the presence of an ADH2*3 allele and expectations of alcohol's effects (p < .01) was uncovered. CONCLUSIONS: These data suggest that the ADH2*3 allele may encode for a more intense response to alcohol, an effect associated with protection from the development of alcohol-use disorders in other populations.

Efectos de la teofilina sobre el tamaño celular y celularidad en ratones BALB/C durante la organogénesis

Se explora el efecto de la administración de 7 mg/kg de peso corporal diarios de teofilina por vía intraperitoneal entre los días 8 y 14 de la preñez en 28 ratones BALB/C sobre el contenido de DNA y proteínas de los fetos al nacer y los estimadores del tamaño y número de células. Los resultados fueron comparados con los de un grupo control de 36 animales. Los resultados indicaron que la teofilina no afectó significativamente el contenido de DNA y proteínas, ni el tamaño y número de células de los fetos.

The effects of the administration of 7 mg/kg of body weight of daily intraperitoneal theophylline, is explored between days 8 and 14 of pregnancy in 28 BALB/C mice, on the DNA and protein contents of the fetuses at birth, and the estimators of size and cell amount. The results were compared with those from a 36 animals control group. Those results indicated that theophylline didn't significantly affect either the DNA and protein contents, or the size and cell amount of the fetuses.

Estudio morfológico de los efectos de la teofilina administrada a ratones BALB/C durante la organogénesis / Morphologic study of the effects of theophylline administered to BALB-C mice during organogenesis

Se explora el efecto de la administración de 7 mg/kg de peso corporal diarios de teofilina por vía intraperitoneal entre los días 8 y 14 de la preñez en 76 ratones BALC/C sobre: tamaño de la camada, número de reabsorciones, peso de los fetos al nacer y ganancia de peso de la madre durante y después del tratamiento. Los resultados fueron comparados con los de un grupo control de 80 animales; no se afectó significativemente ninguna variable reproductiva durante la administración del medicamento, salvo la ganancia de peso corporal de la madre, sí ocurrió, en cambio, una alteración del patrón de asociación de dichas variables cuando se analizaron por separado los animales tratados y los controles (AU)