Open Access Thesis
Date of Award
Sandra W. Jacobson
Alcohol dehydrogenase is a critical enzyme in the metabolism of alcohol. Expression of three alleles at the ADH1B locus results in enzymes that differ in turnover rate and affinity for alcohol. The ADH1B*3 allele, which appears to be unique to African Americans, is associated with more rapid alcohol metabolism than the more prevalent ADH1B*1 allele. It has been previously demonstrated that the presence of at least one maternal ADH1B*3 allele confers a protective effect against alcohol teratogenicity in African American infants and children. This study was conducted to determine whether the presence of the ADH1B*3 allele in the mother or fetus continues to be protective in alcohol-exposed individuals during adolescence. 186 adolescents and 167 mothers participating in the 14-year follow-up of the Detroit Longitudinal Cohort had been genotyped for ADH1B alleles. The frequencies of the ADH1B*3 allele were 17.6% in the mothers and 21.0% in the adolescents, which are consistent with the 22% expected for the African American population. Confirming previous studies, prenatal alcohol exposure was associated with increased attention problems and externalizing behaviors in adolescents born to mothers with two ADH1B*1 alleles but not in those whose mothers had at least one ADH1B*3 allele. The presence of an ADH1B*3 allele in the adolescent conveyed a less pronounced protective effect against fetal alcohol-related deficits at this age. This study is the first to demonstrate that the protective effects of the maternal ADH1B*3 allele continue to be evident during adolescence and suggests that differences in alcohol metabolism genes may help account for individual differences in the vulnerability of offspring to the effects of fetal alcohol exposure. The protective effect of the maternal ADH1B*3 allele may be due to the more rapid metabolism of alcohol that it confers on the mother, which presumably results in a reduction of the peak blood alcohol concentration to which the fetus is exposed during each drinking episode.
Dodge, Neil, "Protective Effects Of The Alcohol Dehydrogenase-Adh1b Allele" (2013). Wayne State University Theses. 228.