Genetic polymorphisms: impact on the risk of fetal alcohol spectrum disorders.
Clinical reports on monozygotic and dizygotic twins provided the initial evidence for the involvement of genetic factors in risk vulnerability for fetal alcohol spectrum disorders (FASD) including fetal alcohol syndrome (FAS). Research with selectively bred and inbred rodents, genetic crosses of these lines and strains, and embryo culture studies have further clarified the role of both maternal and fetal genetics in the development of FASD. Research to identify specific polymorphisms contributing to FASD is still at an early stage. To date, polymorphisms of only one of the genes for the alcohol dehydrogenase enzyme family, the ADH1B, have been demonstrated to contribute to FASD vulnerability. In comparison with ADH1B*1, both maternal and fetal ADH1B*2 have been shown to reduce risk for FAS in a mixed ancestry South African population. ADH1B*3 appears to afford protection for FASD outcomes in African-American populations. Other candidate genes should be examined with respect to FASD risk, including those for the enzymes of serotonin metabolism, in particular the serotonin transporter. By its very nature, alcohol teratogenesis is the expression of the interaction of genes with environment. The study of genetic factors in FASD falls within the new field of ecogenetics. Understanding of the array of genetic factors in FASD will be enhanced by future genetic investigations, including case-control, family association, and linkage studies.
Warren
Kenneth R
KR
Office of Scientific Affairs, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health/DHHS, 5635 Fishers Lane MSC 9304, Bethesda, MD 20892-9304, USA. kw46m@nih.gov
Li
Ting-Kai
TK
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000818:Animals; D000431:Ethanol / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics*; D005333:Fetus / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012377:Rodentia; D014427:Twins / Q000235:genetics
D000431:Ethanol; D000426:Alcohol Dehydrogenase