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

S. H. Kim, Y. M. Kang, S. H. Kim, B. Y. Cho, Y. M. Ye, Gyu Young Hur, H. S. Park

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume64
Issue number2
DOIs
Publication statusPublished - 2009 Feb 1
Externally publishedYes

Fingerprint

Histamine N-Methyltransferase
Urticaria
RNA Stability
Aspirin
Histamine Release
3' Untranslated Regions
Histamine
Basophils
Alleles
Erythrocytes
Genetic Polymorphisms
Mast Cells

Keywords

  • Chronic urticaria patients with aspirin hypersensitivity
  • Genetic polymorphism
  • Histamine N-methyltransferase
  • mRNA stability

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Histamine N-methyltransferase 939A>G polymorphism affects mRNA stability in patients with acetylsalicylic acid-intolerant chronic urticaria. / Kim, S. H.; Kang, Y. M.; Kim, S. H.; Cho, B. Y.; Ye, Y. M.; Hur, Gyu Young; Park, H. S.

In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 64, No. 2, 01.02.2009, p. 213-221.

Research output: Contribution to journalArticle

@article{3b9a0b1e628a446f8f463f9f110cc4f1,
title = "Histamine N-methyltransferase 939A>G polymorphism affects mRNA stability in patients with acetylsalicylic acid-intolerant chronic urticaria",
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.",
keywords = "Chronic urticaria patients with aspirin hypersensitivity, Genetic polymorphism, Histamine N-methyltransferase, mRNA stability",
author = "Kim, {S. H.} and Kang, {Y. M.} and Kim, {S. H.} and Cho, {B. Y.} and Ye, {Y. M.} and Hur, {Gyu Young} and Park, {H. S.}",
year = "2009",
month = "2",
day = "1",
doi = "10.1111/j.1398-9995.2008.01795.x",
language = "English",
volume = "64",
pages = "213--221",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Histamine N-methyltransferase 939A>G polymorphism affects mRNA stability in patients with acetylsalicylic acid-intolerant chronic urticaria

AU - Kim, S. H.

AU - Kang, Y. M.

AU - Kim, S. H.

AU - Cho, B. Y.

AU - Ye, Y. M.

AU - Hur, Gyu Young

AU - Park, H. S.

PY - 2009/2/1

Y1 - 2009/2/1

N2 - 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.

AB - 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.

KW - Chronic urticaria patients with aspirin hypersensitivity

KW - Genetic polymorphism

KW - Histamine N-methyltransferase

KW - mRNA stability

UR - http://www.scopus.com/inward/record.url?scp=58649104880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58649104880&partnerID=8YFLogxK

U2 - 10.1111/j.1398-9995.2008.01795.x

DO - 10.1111/j.1398-9995.2008.01795.x

M3 - Article

VL - 64

SP - 213

EP - 221

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

SN - 0105-4538

IS - 2

ER -