Contribution of the OBSCN Nonsynonymous Variants to Aspirin Exacerbated Respiratory Disease Susceptibility in Korean Population
- Title
- Contribution of the OBSCN Nonsynonymous Variants to Aspirin Exacerbated Respiratory Disease Susceptibility in Korean Population
- Author
- 고인송
- Keywords
- OBSTRUCTIVE PULMONARY-DISEASE; AIRWAY SMOOTH-MUSCLE; SARCOPLASMIC-RETICULUM; GENE POLYMORPHISMS; INTOLERANT ASTHMA; ASSOCIATION; DIAGNOSIS; OBSCURIN; HYPERSENSITIVITY; PATHOGENESIS
- Issue Date
- 2012-05
- Publisher
- Mary Ann Liebert, Inc.
- Citation
- DNA and cell biology, 2012, 31(6), P.1001-1009
- Abstract
- Airway remodeling and exacerbated airway narrowing in asthma have been attributed to the regulation of intracellular Ca2+ by sarcoplasmic reticulum (SR) of the airway smooth muscle cells. The protein encoded by obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF (OBSCN) is a crucial factor in determining the SR architecture in Obscn−/− mice. This study genotyped a total of 55 common single-nucleotide polymorphisms (SNPs) in 592 Korean asthmatics including 163 aspirin exacerbated respiratory disease (AERD) cases and 429 aspirin-tolerant asthma (ATA) controls. Eight SNPs, including two nonsynonymous polymorphisms rs1188722C>T (Leu2116Phe) and rs1188729G>C (Cys4642Ser), and one haplotype BL2_ht1 showed statistically significant associations with AERD development (p=0.003–0.03). Two variants, rs1188722C>T (Leu2116Phe) and rs369252C>A, also revealed nominal association with FEV1 decline by aspirin provocation in asthmatics (p=0.03–0.04). Intriguingly, rs1188722C>T (Leu2116Phe) is a highly conserved amino acid residue among species, suggesting its functional relevance to AERD. In addition, the A allele of rs369252C>A, which was more prevalent in AERD than in ATA, was predicted as a potential branch point (BP) site for alternative splicing (BP score=4.29). Although further functional evaluation is required, our findings suggest that OBSCN polymorphisms, in particular, highly conserved nonsynonymous Leu2116Phe variant, might contribute to aspirin hypersensitivity in asthmatics.
- URI
- https://www.liebertpub.com/doi/abs/10.1089/dna.2011.1436https://repository.hanyang.ac.kr/handle/20.500.11754/70137
- ISSN
- 1044-5498
- DOI
- 10.1089/dna.2011.1436
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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