Association of the variants in AGT gene with modified drug response in Korean aspirin-intolerant asthma patients |
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Authors: | Pasaje Charisse Flerida A Kim Jeong-Hyun Park Byung-Lae Cheong Hyun Sub Park Tae-Joon Lee Jin-Sol Kim Yongha Bae Joon Seol Kim Jin Moo Park Jong Sook Park Choon-Sik Shin Hyoung Doo |
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Institution: | aDepartment of Life Science, Sogang University, 1 Shinsu-dong, Mapo-gu, Seoul 121-742, Republic of Korea;bDepartment of Genetic Epidemiology, SNP Genetics, Inc., Seoul 153-803, Republic of Korea;cGenome Research Center for Allergy and Respiratory Diseases, Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 420-767, Republic of Korea |
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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; Pcorr = 0.02–0.03). Furthermore, the two variants also exhibited associations with MLK response rate (P = 0.0003–0.0006; Pcorr = 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. |
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Keywords: | Aspirin-intolerant asthma AGT MLK Polymorphism Haplotype |
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