Alcohol dehydrogenase 2*3 affects alterations in offspring facial morphology associated with maternal ethanol intake in pregnancy.
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.
Das
Utpala G
UG
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Cronk
Christine E
CE
Martier
Susan S
SS
Simpson
Pippa M
PM
McCarver
D Gail
DG
D000293:Adolescent; D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D005146:Facial Asymmetry / Q000151:congenital / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018709:Statistics, Nonparametric
C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C020145:formaldehyde dehydrogenase (glutathione); D000445:Aldehyde Oxidoreductases