Involvement of human histamine N-methyltransferase gene polymorphisms in susceptibility to atopic dermatitis in korean children.
OBJECTIVE
Histamine N-methyltransferase (HNMT) catalyzes one of two major histamine metabolic pathways. Histamine is a mediator of pruritus in atopic dermatitis (AD). The aim of this study was to evaluate the association between HNMT polymorphisms and AD in children.


METHODS
We genotyped 763 Korean children for allelic determinants at four polymorphic sites in the HNMT gene: -465T>C, -413C>T, 314C>T, and 939A>G. Genotyping was performed using a TaqMan fluorogenic 5' nuclease assay. The functional effect of the 939A>G polymorphism was analyzed.


RESULTS
Of the 763 children, 520 had eczema and 542 had atopy. Distributions of the genotype and allele frequencies of the HNMT 314C>T polymorphism were significantly associated with non-atopic eczema (P=0.004), and those of HNMT 939A>G were significantly associated with eczema in the atopy groups (P=0.048). Frequency distributions of HNMT -465T>C and -413C>T were not associated with eczema. Subjects who were AA homozygous or AG heterozygous for 939A>G showed significantly higher immunoglobulin E levels than subjects who were GG homozygous (P=0.009). In U937 cells, the variant genotype reporter construct had significantly higher mRNA stability (P<0.001) and HNMT enzyme activity (P<0.001) than the common genotype.


CONCLUSIONS
Polymorphisms in HNMT appear to confer susceptibility to AD in Korean children.
Department of Pediatrics and Institute of Allergy, Severance Biomedical Science Institute, BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Hee Seon
HS
Lee
Seung-Hyun
SH
Kim
Kyung Won
KW
Kim
Ji Young
JY
Baek
Hae-Sim
HS
Park
Kyung Eun
KE
Lee
Jung Yeon
JY
Hong
Mi Na
MN
Kim
Won Il
WI
Heo
Myung Hyun
MH
Sohn
Kyu-Earn
KE
Kim