Involvement of Human Histamine N-methyltransferase Gene Polymorphisms in Susceptibility to Atopic Dermatitis in Korean Children

Abstract

Histamine N-methyltransferase (HNMT) catalyzes one of two major metabolic pathways for histamine. Histamine is one of the mediators for pruritus of atopic dermatitis. The aim of this study was to evaluate the role of HNMT polymorphisms in children with atopic dermatitis. We genotyped 763 children for allelic determinants at four polymorphic sites, which were -465T>C, -413C>T, 314C>T and 939A>G in the HNMT gene, and the functional effect of the 939A>G polymorphism was analyzed. The genotyping was screened using the TaqMan fluorogenic 5’ nuclease assay (ABI, Foster City, CA, USA). Among these 763 children, 520 had eczema and 542 had atopy. Distributions of the genotype and allele frequencies of HNMT 314C>T polymorphism were significantly associated with non-atopic eczema (P = .004) and those of HNMT 939A>G polymorphism were significantly associated with eczema in atopy groups (P = .048). However, those of HNMT 654T>C and 413C>T polymorphisms were not. In addition, subjects with the homozygous AA or heterozygous AG of the 939A>G polymorphism showed significantly higher IgE levels than those with the homozygous GG genotype (P = .009). In U937 cells, the variant genotype reporter construct showed significantly higher mRNA stability (P < .001) and HNMT enzyme activity (P < .001) than the common genotype. Polymorphisms in the HNMT gene appear to confer susceptibility to atopic dermatitis in Korean children.