Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma
Autor: | Heung-Woo Park, Jong Eun Lee, Young Min Ye, Yoon-Keun Kim, Sang-Heon Kim, Sang Hoon Kim, Young Koo Jee, Hae-Sim Park, Seung-Hyun Kim, Kyung Up Min, Yoon-Seok Chang, Eun Soon Shin, Joon Woo Bahn |
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Rok vydání: | 2007 |
Předmět: |
Adult
Male Candidate gene Linkage disequilibrium Genotype Receptors Prostaglandin Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Thromboxane receptor Gene Frequency Genetics Genetic predisposition Humans General Pharmacology Toxicology and Pharmaceutics Molecular Biology Allele frequency Genetics (clinical) Alleles Korea Aspirin Haplotype Drug Tolerance Middle Aged Asthma Phenotype Haplotypes Pharmacogenetics Case-Control Studies Immunology Prostaglandins Molecular Medicine Female |
Zdroj: | Pharmacogenetics and genomics. 17(4) |
ISSN: | 1744-6872 |
Popis: | Background Genetic predisposition is linked to the pathogenesis of aspirin-intolerant asthma. Most candidate gene approaches have focused on leukotriene-related pathways, whereas there have been relatively few studies evaluating the effects of polymorphisms in prostanoid receptor genes on the development of aspirin-intolerant asthma. Therefore, we investigated the potential association between prostanoid receptor gene polymorphisms and the aspirin-intolerant asthma phenotype. Methods We screened for genetic variations in the prostanoid receptor genes PTGER1, PTGER2, PTGER3, PTGER4, PTGDR, PTGIR, PTGFR, and TBXA2R using direct sequencing, and selected 32 tagging single nucleotide polymorphisms among the 77 polymorphisms with frequencies >0.02 based on linkage disequilibrium for genotyping. We compared the genotype distributions and allele frequencies of three participant groups (108 patients with aspirin-intolerant asthma, 93 patients with aspirin-tolerant asthma, and 140 normal controls). Results Through association analyses studies of the 32 single nucleotide polymorphisms, the following single nucleotide polymorphisms were found to have significant associations with the aspirin-intolerant asthma phenotype: -616C>G (P=0.038) and -166G>A (P=0.023) in PTGER2; -1709T>A (P=0.043) in PTGER3; -1254A>G (P=0.018) in PTGER4; 1915T>C (P=0.015) in PTGIR; and -4684C>T (P=0.027), and 795T>C (P=0.032) in TBXA2R. In the haplotype analysis of each gene, the frequency of PTGIR ht3[G-G-C-C], which includes 1915T>C, differed significantly between the aspirin-intolerant asthma patients and aspirin-tolerant asthma patients (P=0.015). Conclusion These findings suggest that genetic polymorphisms in PTGER2, PTGER3, PTGER4, PTGIR, and TBXA2R play important roles in the pathogenesis of aspirin-intolerant asthma. |
Databáze: | OpenAIRE |
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