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 (P¼0.002-0.04), 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 (P¼0.02-0.04). However, TAP1 polymorphisms showed no relations to both AERD and FEV1 decline after aspirin challenge (P40.05). 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.

Associations of TAP1 genetic polymorphisms with atopic diseases: asthma, rhinitis and dermatitis

“…Subsequently, 126 articles were excluded due to duplication (n=24) or without relation to this topic (n=102). Following detailed evaluation of the remaining twelve studies, four studies were excluded with one being lack of relation to rs1057141 or rs1135216 polymorphism [ 15 ], one not being a case-control study [ 16 ], and two lack of enough pertinent data [ 8 , 14 ]. A total of 8 articles, with 7 published in English and 1 in Chinese, were included for qualitative synthesis based on the inclusion and exclusion criteria [ 5 – 7 , 9 – 13 ].…”

Association analysis of tapasin polymorphisms with aspirin-exacerbated respiratory disease in asthmatics

“…As there are considerable variability and extensive LD throughout the HLA region, identification of causal variants for diseases within the HLA has remained difficult. We have already published an association of SNPs on TAP2, TAP1 [17], HLA-DPB1 [43], and WDR46 [44] with AERD in asthmatics. As seen in LD blocks between these genes (Supplementary Fig.…”

“…SNP of TAP1 was found to be associated with atopy [16]. In addition, we have found that SNPs and haplotypes of TAP1 and TAP2 are associated with aspirin-induced bronchospasm [17]. However, SNPs of the TAPBP gene have not been evaluated with respect to the development of AERD.…”

CNest: A Novel Copy Number Association Discovery Method Uncovers 862 New Associations from 200,629 Whole Exome Sequence Datasets in the UK Biobank

“…Unsurprisingly the strongest signal for asthma is found in the HLA with the lead signal specifically restricted to the HLA-DQA2 gene which has strong prior associations to asthma and hay fever all based on intergenic SNPs from multiple SNP based GWAS investigations (95)(96)(97)(98)(99). Some of our novel CNV associations for asthma (Supplementary Table 5) include signals in genes, TAP2 and STARD3NL, which have not been linked with asthma by previous SNP GWAS studies but have evidence of association to certain other respiratory diseases (100,101).…”