Protective effects of the alcohol dehydrogenase-ADH1B*3 allele on attention and behavior problems in adolescents exposed to alcohol during pregnancy
Protective effects of the alcohol dehydrogenase-ADH1B*3 allele on attention and behavior problems in adolescents exposed to alcohol during pregnancy
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DOI：
10.1016/j.ntt.2013.11.003
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发表时间：
2014-01-01
影响因子：
2.9
通讯作者：
Jacobson, Sandra W.
中科院分区：
文献类型：
--
作者：
Dodge, Neil C.;Jacobson, Joseph L.;Jacobson, Sandra W.
乙醇脱氢酶是酒精代谢的关键酶。ADH1B基因座上三个等位基因的表达导致酶的周转率和对酒精的亲和力不同。ADH1B*3等位基因似乎是非洲人后裔所特有的，与更普遍的ADH1B*1等位基因相比，它与更快的酒精代谢有关。先前已经证明，至少一个母体ADH1B*3等位基因的存在对婴儿和儿童酒精致畸具有保护作用。本研究旨在确定母亲或儿童中ADH1B*3等位基因的存在是否在青春期酒精暴露个体中继续起保护作用。参与底特律纵向队列14年随访的186名青少年和167名母亲对ADH1B等位基因进行了基因分型。从任课教师处获得行为报告。ADH1B*3等位基因在母亲中的频率为17.6%，在青少年中的频率为21.0%，这与非洲裔美国人预期的15-20%一致。产前酒精暴露与母亲有两个ADH1B*1等位基因的青少年的注意力问题和外化行为增加有关，但与母亲至少有一个ADH1B*3等位基因的青少年无关。在青少年中，ADH1B*3等位基因的存在或缺失也出现了类似的模式，这可能反映了母体变异的存在/缺失。这项研究首次证明了母体ADH1B*3等位基因的保护作用在青春期继续明显。这些持续存在的个体差异对胎儿酒精暴露行为影响的脆弱性可能归因于ADH1B*3变异赋予母亲更快的酒精代谢，导致胎儿在每次饮酒期间暴露的血液酒精浓度峰值降低。(C) 2013 Elsevier Inc .版权所有
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 individuals of African descent, 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 infants and children. This study was conducted to determine whether the presence of the ADH1B*3 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 ADH1B*3 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 ADH1B*1 alleles but not in those whose mothers had at least one ADH1B*3 allele. A similar pattern was seen in relation to the presence or absence of an ADH1B*3 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 ADH1B*3 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 ADH1B*3 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. (C) 2013 Elsevier Inc All rights reserved.