Association of the variants in AGT gene with modified drug response in Korean aspirin-intolerant asthma patients.

Abstract

The angiotensinogen (AGT) gene enhances the effect of several bronchoconstrictors and produces a peptide that is accumulated in the airways of asthma patients; events that may underpin the pathogenesis of aspirin-intolerant asthma (AIA). To carry out a case-control analysis between AGT and aspirin-induced bronchospasm following treatment with an anti-asthma drug, montelukast (MLK), 38 single nucleotide polymorphisms (SNPs) in AGT were genotyped in 56 AIA cohort. Genotyping was performed with TaqMan assay and haplotypes were inferred using PHASE algorithm ver. 2.0. Statistical analyses of each SNPs and haplotypes were performed using SAS version 9.1. Among 13 variants displaying significant signals, two SNPs (+2401C>G and +2476C>T) in the intronic region of AGT were significantly associated with modification of drug response even after correction for multiple testing (P=0.0009-0.002; P(corr)=0.02-0.03). Furthermore, the two variants also exhibited associations with MLK response rate (P=0.0003-0.0006; P(corr)=0.006-0.01). Although our results are preliminary and further replication in a larger-scale group of subjects should be warranted, these observations provide evidence that AGT variants might be one of genetic factors involved in the response of anti-asthma drugs in AIA patients.

• Authors: Charisse Flerida A Pasaje, Jeong-Hyun Kim, Byung-Lae Park, Hyun Sub Cheong, Tae-Joon Park, Jin-Sol Lee, Yongha Kim, Joon Seol Bae, Jin Moo Kim, Jong Sook Park, Choon-Sik Park, Hyoung Doo Shin
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 24 Issue 5 Pg. 595-601 (Oct 2011) ISSN: 1522-9629 [Electronic] England
• PMID: 21624492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Acetates
• Anti-Asthmatic Agents
• Cyclopropanes
• Quinolines
• Sulfides
• Angiotensinogen
• montelukast
• Aspirin

Topics

• Acetates (pharmacology)
• Adolescent
• Adult
• Aged
• Algorithms
• Angiotensinogen (genetics)
• Anti-Asthmatic Agents (pharmacology)
• Asian People (genetics)
• Aspirin (adverse effects, immunology)
• Asthma, Aspirin-Induced (drug therapy, genetics)
• Bronchial Spasm (chemically induced)
• Case-Control Studies
• Cyclopropanes
• Drug Hypersensitivity (genetics)
• Female
• Genetic Predisposition to Disease
• Genetic Variation
• Genotype
• Haplotypes
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Quinolines (pharmacology)
• Republic of Korea
• Sulfides
• Young Adult