title: Genetic association analysis of TAP1 and TAP2 polymorphisms with aspirin exacerbated respiratory disease and its FEV1 decline.
abstract: Aspirin exacerbated respiratory disease (AERD) induces bronchoconstriction in asthmatic patients characterized with a clinical condition of severe decline in forced expiratory volume in one second (FEV1) after ingestion of aspirin. Two genes consisting a heterodimer, transporter 1 and 2, ATP-binding cassette, sub-family B (MDR/TAP) (TAP1 and TAP2) within the major histocompatibility complex (MHC) region, have been implicated in immunodeficiency and bronchiectasis development. To investigate the associations of TAP1 and TAP2 genetic polymorphisms with AERD and phenotypic FEV1 decline, a total of 43 common single-nucleotide polymorphisms (SNPs) including 12 SNPs of TAP1 and 31 SNPs of TAP2 were genotyped in 93 AERD patients and 96 aspirin-tolerant asthma controls. Interestingly, regression analysis revealed that polymorphisms and haplotypes of TAP2 were associated with FEV1 decline by aspirin provocation (P=0.002-0.04), with about twofold decline rate of FEV1 in most of minor homozygotes compared with major homozygotes. In addition, nominal evidences of association between TAP2 and AERD development were observed (P=0.02-0.04). However, TAP1 polymorphisms showed no relations to both AERD and FEV1 decline after aspirin challenge (P>0.05). Although further functional evaluations and replications are required, our preliminary findings provide supporting information that variants of TAP2 might be predisposing factors for FEV1 decline-related symptoms.
authors.affiliation: Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Charisse Flerida A
authors.initials: CF
authors.lastname: Pasaje
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Jong Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Inseon S
authors.initials: IS
authors.lastname: Choi
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D055963:Asthma, Aspirin-Induced / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D001985:Bronchial Provocation Tests; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D056910:Republic of Korea; D055815:Young Adult
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D001241:Aspirin