Purpose of the Study
A case control study was performed to determine the differences in the distribution of mutation frequency and genotypes that encode normal and defective activity of N-acetyltransferase in children with atopic allergies compared with healthy children. Previous studies in persons with chronic allergic rhinitis have shown an overrepresentation of phenotypically slow acetylators. This was the first timeNAT2 genotype, which unlike the acetylation phenotype is not affected by environmental factors, has been used to evaluate the role of the genetic amine acetylation defect in the pathogenesis of allergic disease.
Genotypes were determined from 56 children with documented inhalation, food, or mixed allergies and from 100 healthy control children with no clinical or laboratory signs of allergy. All subjects were white children from central Poland with a mean age of 3.89 ± 6.4 years.
DNA was isolated from 1- to 2-mL samples of blood. Polymerase chain reaction followed by analysis of restriction fragment length polymorphism identified genotype coding forN-acetyltransferase. To disclose genotypes that determine fast and slow acetylation phenotypes in white individuals, four of seven known NAT2 gene mutations were identified. The three other mutations in this region either have not yet been found in white individuals or occur in tandem with one of the identified mutations.
Among the total population (n = 156) 351 mutations were found in the NAT2 gene. A statistically significant difference in the distribution of the frequency of mutated alleles between the case and control groups was shown. Ninety-one percent of children from the case group had genotypes that determined slow acetylation phenotypes. In contrast, 38% of the control group had rapid acetylation genotypes (normal NAT2 activity) and 62% had genotypes with mutated alleles (homozygous or heterozygous).
The majority of subjects studied had genotypes that included mutated alleles of the NAT2 gene. The authors remind usNAT2 mutations are associated with acetylation defects, and acetylation has been hypothesized to play an important role in the inactivation of excessively released histamine, the primary mediator of atopic allergic reactions. They conclude that genetic defect of acetylation may be treated as a marker of atopic predisposition.
As the authors acknowledge in their discussion, histamine is only one of many inflammatory process mediators released in allergic reactions. Additional studies are needed to evaluate the importance of their findings in relation to clinical manifestations.