N-acetyltransferase 2 polymorphisms and susceptibility to infant leukemia with maternal exposure to dipyrone during pregnancy.
BACKGROUND
Maternal exposure to dipyrone during pregnancy has been associated with risk of infant leukemia (IL). N-Acetyltransferase 2 (NAT2) enzyme acetylates dipyrone, resulting in a detoxified metabolite. We performed genotyping to identify the distribution of NAT2 polymorphisms in duo samples from mothers and children previously investigated in a case-controlled study of IL.


METHODS
Samples from 132 IL, 131 age-matched controls, mothers of cases (n = 86), and mothers of controls (n = 36) were analyzed. PCR-RFLP assays were used to determine the NAT2 variants 191G>A, 282C>T, 341T>C, 481C>T, 590G>A, 803A>G, and 857G>A. The test for case-control differences in the distribution of genotypes was based on χ(2) statistics. Unconditional logistic regression was used to examine the association between maternal exposure to dipyrone during the index pregnancy, IL, and NAT2 phenotypes. Crude and adjusted odds ratios (OR) are given with the 95% confidence interval (95% CI).


RESULTS
NAT2 slow-acetylation haplotypes were associated with IL (OR, 8.90; 95% CI, 1.71-86.7). An association between IL and NAT2 phenotype was observed in IL whether the mothers reported dipyrone exposures (OR, 4.48; 95% CI, 1.88-10.7) or not (OR, 4.27; 95% CI, 1.75-10.5). The combination of NAT2 slow/slow (mother/child) phenotypes confers a higher risk of IL (OR, 30.0; 95% CI, 5.87-279.7).


CONCLUSIONS
NAT2 slow-acetylation profiles are associated with IL regardless of maternal exposure to dipyrone during pregnancy.


CONCLUSIONS
Further recommendations about medicine exposures during pregnancy should take into account that infants with the maternal NAT2 slow-acetylation genotypes might be particularly vulnerable to greater risk.
Zanrosso
Crisiane Wais
CW
Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Emerenciano
Mariana
M
Gonçalves
Bruno Alves de Aguiar
BA
Faro
Alessandra
A
Koifman
Sérgio
S
Pombo-de-Oliveira
Maria S
MS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D004177:Dipyrone / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000139:chemically induced / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004177:Dipyrone; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human