Periconceptional multivitamin intake during early pregnancy, genetic variation of acetyl-N-transferase 1 (NAT1), and risk for orofacial clefts.
BACKGROUND
Periconceptional supplementation of multivitamins that include folic acid have been shown to prevent several birth defects, including neural tube defects and orofacial clefts. We investigated whether polymorphic variants of fetal acetyl-N-transferase 1 (NAT1), an enzyme involved in the catabolism of folates, differentially interacted with maternal multivitamin use during early pregnancy to alter the risk of delivering an infant with an orofacial cleft malformation.


METHODS
Using a large population-based case-control study, we genotyped 421 California infants born with an isolated cleft and 299 controls for two NAT1 polymorphisms.


RESULTS
Compared to the homozygous wild-type genotypes, odds ratios for isolated cleft lip with/without cleft palate were slightly increased among infants who were homozygous for the variant alleles of NAT1 1088 and 1095. For isolated cleft palate, no similar associations with these two NAT1 variants were observed. For NAT1 1088 genotypes, we did not observe any differential risks for clefts related to maternal multivitamin intake. For NAT1 1095 genotypes, however, we found a two-fold higher risk for isolated cleft lip with/without cleft palate among infants who were homozygous for the variant allele and whose mothers did not take multivitamins during early pregnancy.


CONCLUSIONS
We found evidence suggestive of an interaction between the NAT1 1095 polymorphism and lack of maternal multivitamin use that increased risks of isolated cleft lip with/without cleft palate.
Lammer
Edward J
EJ
Children's Hospital Research Institute, Oakland, California 94609, USA. elammer@chori.org
Shaw
Gary M
GM
Iovannisci
David M
DM
Finnell
Richard H
RH
D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D002971:Cleft Lip / Q000201:enzymology / Q000235:genetics*; D002972:Cleft Palate / Q000201:enzymology / Q000235:genetics*; D015331:Cohort Studies; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007527:Isoenzymes; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D016742:Preconception Care; D011247:Pregnancy; D012307:Risk Factors
D007527:Isoenzymes; D005492:Folic Acid; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1