title: Association analysis of member RAS oncogene family gene polymorphisms with aspirin intolerance in asthmatic patients.
abstract: Member RAS oncogene family (RAB1A), a member of the RAS oncogene family, cycles between inactive GDP-bound and active GTP-bound forms regulating vesicle transport in exocytosis. Thus, functional alterations of the RAB1A gene may contribute to aspirin intolerance in asthmatic sufferers. To investigate the relationship between single-nucleotide polymorphisms (SNPs) in the RAB1A gene and aspirin-exacerbated respiratory disease (AERD), asthmatics (n=1197) were categorized into AERD and aspirin-tolerant asthma (ATA). All subjects were diagnosed as asthma on the basis of the Global Initiative for Asthma (GINA) guidelines. AERD was defined as asthmatics showing 15% or greater decreases in forced expiratory volume in one second (FEV(1)) or naso-ocular reactions by the oral acetyl salicylic acid (ASA) challenge (OAC) test. In total, eight SNPs were genotyped. Logistic regression analysis identified that the minor allele frequency of +14444 T>G and +41170 C>G was significantly higher in the AERD group (n=181) than in the ATA group (n=1016) (p=0.0003-0.03). Linear regression analysis revealed a strong association between the SNPs and the aspirin-induced decrease in FEV(1) (p=0.0004-0.004). The RAB1A gene may play a role in the development of AERD in asthmatics and the genetic polymorphisms of the gene have the potential to be used as an indicator of this disease.
authors.affiliation: 1 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital , Bucheon, Republic of Korea.
authors.forename: Jong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Heo
authors.forename: Hun Soo
authors.initials: HS
authors.lastname: Chang
authors.forename: Inseon S
authors.initials: IS
authors.lastname: Choi
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Jong-Uk
authors.initials: JU
authors.lastname: Lee
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D004361:Drug Tolerance; D005260:Female; D005787:Gene Frequency; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D017931:DNA Primers; D001241:Aspirin