Dodge Neil C, Jacobson Joseph L, Jacobson Sandra W
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA; Department of Human Biology, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Department of Psychiatry and Mental Health, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.
Neurotoxicol Teratol. 2014 Jan-Feb;41:43-50. doi: 10.1016/j.ntt.2013.11.003. Epub 2013 Nov 19.
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 ADH1B3 allele, which appears to be unique to individuals of African descent, is associated with more rapid alcohol metabolism than the more prevalent ADH1B1 allele. It has been previously demonstrated that the presence of at least one maternal ADH1B3 allele confers a protective effect against alcohol teratogenicity in infants and children. This study was conducted to determine whether the presence of the ADH1B3 allele in the mother or child continues to be protective in alcohol-exposed individuals during adolescence. 186 adolescents and 167 mothers participating in a 14-year follow-up of the Detroit Longitudinal Cohort were genotyped for ADH1B alleles. Behavioral reports were obtained from classroom teachers. Frequencies of the ADH1B3 allele were 17.6% in the mothers and 21.0% in the adolescents, which are consistent with the 15-20% expected for African Americans. Prenatal alcohol exposure was associated with increased attention problems and externalizing behaviors in adolescents born to mothers with two ADH1B1 alleles but not in those whose mothers had at least one ADH1B3 allele. A similar pattern was seen in relation to the presence or absence of an ADH1B3 allele in the adolescent, which may have reflected the presence/absence of the maternal variant. This study is the first to demonstrate that the protective effects of the maternal ADH1B3 allele continue to be evident during adolescence. These persistent individual differences in vulnerability of offspring to the behavioral effects of fetal alcohol exposure are likely attributable to more rapid metabolism of alcohol that the ADH1B3 variant confers on the mother, leading to a reduction of the peak blood alcohol concentration to which the fetus is exposed during each drinking episode.
乙醇脱氢酶是酒精代谢中的一种关键酶。ADH1B基因座上三个等位基因的表达产生了周转率和对酒精亲和力不同的酶。ADH1B3等位基因似乎是非洲裔个体所特有的，与比更常见的ADH1B1等位基因更快的酒精代谢有关。先前已经证明，至少一个母亲的ADH1B3等位基因的存在对婴儿和儿童的酒精致畸性具有保护作用。本研究旨在确定母亲或儿童中ADH1B3等位基因的存在在青春期接触酒精的个体中是否仍然具有保护作用。对参与底特律纵向队列14年随访的186名青少年和167名母亲进行了ADH1B等位基因的基因分型。从课堂教师那里获得行为报告。母亲中ADH1B3等位基因的频率为17.6%，青少年中为21.0%，这与非裔美国人预期的15 - 20%一致。产前酒精暴露与母亲有两个ADH1B1等位基因的青少年的注意力问题增加和外化行为有关，但在母亲至少有一个ADH1B3等位基因的青少年中则不然。在青少年中ADH1B3等位基因的有无方面也观察到了类似的模式，这可能反映了母亲变体的有无。这项研究首次证明母亲的ADH1B3等位基因的保护作用在青春期仍然明显。后代对胎儿酒精暴露行为影响的易感性存在这些持续的个体差异，可能归因于ADH1B3变体赋予母亲的更快的酒精代谢，导致每次饮酒期间胎儿接触的血液酒精浓度峰值降低。
