title: Genome-wide association study of aspirin-exacerbated respiratory disease in a Korean population.
abstract: Aspirin-exacerbated respiratory disease (AERD) is a nonallergic clinical syndrome characterized by a severe decline in forced expiratory volume in one second (FEV1) following the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin. The effects of genetic variants have not fully explained all of the observed individual differences to an aspirin challenge despite previous attempts to identify AERD-related genes. In the present study, we performed genome-wide association study (GWAS) and targeted association study in Korean asthmatics to identify new genetic factors associated with AERD. A total of 685 asthmatic patients without AERD and 117 subjects with AERD were used for the GWAS of the first stage, and 996 asthmatics without AERD and 142 subjects with AERD were used for a follow-up study. A total of 702 SNPs were genotyped using the GoldenGate assay with the VeraCode microbead. GWAS revealed the top-ranked variants in 3' regions of the HLA-DPB1 gene. To investigate the detailed genetic effects of an associated region with the risk of AERD, a follow-up targeted association study with the 702 single nucleotide polymorphisms (SNPs) of 14 genes was performed on 802 Korean subjects. In a case-control analysis, HLA-DPB1 rs1042151 (Met105Val) shows the most significant association with the susceptibility of AERD (p = 5.11 × 10(-7); OR = 2.40). Moreover, rs1042151 also shows a gene dose for the percent decline of FEV1 after an aspirin challenge (p = 2.82 × 10(-7)). Our findings show that the HLA-DPB1 gene polymorphism may be the most susceptible genetic factor for the risk of AERD in Korean asthmatics and confirm the importance of HLA-DPB1 in the genetic etiology of AERD.
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc, Seoul, Republic of Korea.
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Charisse Flerida A
authors.initials: CF
authors.lastname: Pasaje
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Lyoung Hyo
authors.initials: LH
authors.lastname: Kim
authors.forename: Jong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Lee
authors.forename: Myung-Sin
authors.initials: MS
authors.lastname: Kim
authors.forename: Inseon S
authors.initials: IS
authors.lastname: Choi
authors.forename: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: SeungWoo
authors.initials: S
authors.lastname: Shin
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; D044466:Asian People / Q000706:statistics & numerical data*; D055963:Asthma, Aspirin-Induced / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D002648:Child; D005260:Female; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D059868:HLA-DP beta-Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors
chemical_list: D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen