RESUMO
BACKGROUND: Ethanol intake during pregnancy alters offspring facial morphology. However, significant variation that may be due to genetic diversity in ethanol metabolizing enzymes occurs. The alcohol dehydrogenase 1B*3 (ADH1B*3) allele is protective for offspring developmental outcome after maternal alcohol drinking in pregnancy and may explain the spectrum of facial morphology. METHODS: Faces of infants with known ADH1B genotype, whose mothers' ADH1B genotypes and ethanol intake were determined during pregnancy, were photographed using uniform procedures. Photographs were scanned and the inner canthal distance, palpebral fissure length, and distance from the bridge of the nose to the bottom of the upper lip were measured by an investigator who was blinded to genotype and ethanol exposure. RESULTS: Among 247 photographed infants, each facial measurement varied >2-fold. Median absolute ethanol daily intake was 0.5 oz among mothers who reported drinking in the periconceptional period (N = 173) and 0.17 oz among mothers who reported drinking before the first prenatal visit (N = 62). Controlling for the amount of maternal ethanol intake just before the first prenatal visit and infant sex, the three-way interaction among the absence of a maternal and offspring ADH1B*3 allele and the presence of ethanol consumption just before the first prenatal visit was associated with smaller facial measurements (p = 0.002, MANCOVA). CONCLUSIONS: These are the first observations of a significant gene-environment interaction explaining variation in facial morphology associated with ethanol use in pregnancy. This positive effect of ADH1B*3 is consistent with its known positive effect on offspring birth weight and developmental outcome after in utero ethanol exposure.
Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/genética , Aldeído Oxirredutases/genética , Assimetria Facial/enzimologia , Assimetria Facial/genética , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/metabolismo , Análise de Variância , Distribuição de Qui-Quadrado , Assimetria Facial/congênito , Assimetria Facial/epidemiologia , Feminino , Humanos , Lactente , Gravidez , Estatísticas não ParamétricasRESUMO
Absence of AMP-deaminase was demonstrated by histochemical and biochemical methods in a muscle biopsy of a 25-year-old woman with facial and limb girdle myopathy. Venous ammonia failed to rise after ischaemic exercise. This patient further contributes to the variety of clinical pictures associated with AMP-deaminase deficiency. Whereas AMP-deaminase has been shown to play an essential role in the regulation of adenine nucleotide metabolism in the liver, its physiological function in muscle remains uncertain.