27 323

Cited 0 times in

Histamine N-methyltransferase 939A>G polymorphism affects mRNA stability in patients with acetylsalicylic acid-intolerant chronic urticaria.

Authors
Kim, SH; Kang, YM; Cho, BY; Ye, YM; Hur, GY; Park, HS
Citation
Allergy, 64(2):213-221, 2009
Journal Title
Allergy
ISSN
0105-45381398-9995
Abstract
BACKGROUND: Histamine plays an important role in allergic inflammation. Histamine levels are regulated by histamine N-methyltransferase (HNMT).



OBJECTIVE: To investigate the functional variability of HNMT gene in relation to genetic polymorphisms in patients with aspirin intolerant chronic urticaria (AICU).



METHODS: Two single-nucleotide polymorphisms of the HNMT gene (314C>T, 939A>G) were genotyped in chronic urticaria patients. The functional variability of 3'-untranslated region polymorphism (3'-UTR) was assessed using the pEGFP-HNMT 3'-UTR reporter construct to examine mRNA stability and fluorescence-tagged protein expression. The HNMT enzymatic activities related to the 939A>G polymorphism were examined both in the human mast cells (HMC-1) transfected with the pHNMT CDS-3'-UTR construct and in the patients' red blood cells (RBCs). Histamine release from the basophils of AICU patients was examined.



RESULTS: The 939A>G polymorphism was significantly associated with the AICU phenotype, while no association was found with the 314C>T polymorphism. An in vitro functional study using HMC-1 cells demonstrated that the 939A allele gave lower levels of HNMT mRNA stability, HNMT protein expression, and HNMT enzymatic activity and higher histamine release than the 939G allele. The in vivo functional study demonstrated that the AICU patients with the 939A allele had lower HNMT activity in RBC lysates and higher histamine release from their basophils.



CONCLUSION: The HNMT 939A>G polymorphism lowers HNMT enzymatic activity by decreasing HNMT mRNA stability, which leads to an increase in the histamine level and contributes to the development of AICU.
MeSH terms
AdultAllelesAnti-Inflammatory Agents, Non-Steroidal/adverse effects*Anti-Inflammatory Agents, Non-Steroidal/immunologyAspirin/adverse effects*Aspirin/immunologyBasophils/immunologyBasophils/metabolismCase-Control StudiesChronic DiseaseErythrocytes/immunologyErythrocytes/metabolismFemaleGene FrequencyGenetic Predisposition to DiseaseGenotypeHistamine N-Methyltransferase/genetics*Histamine N-Methyltransferase/immunologyHistamine N-Methyltransferase/metabolismHistamine Release/geneticsHistamine Release/immunologyHumansMaleMiddle AgedPolymorphism, Single NucleotideRNA Stability/genetics*Urticaria/drug therapyUrticaria/genetics*Urticaria/immunology
DOI
10.1111/j.1398-9995.2008.01795.x
PMID
19178400
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
AJOU Authors
예, 영민박, 해심
Full Text Link
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse