Putative association of SMAPIL polymorphisms with risk of aspirin intolerance in asthmatics

Abstract

Background. Aspirin-intolerant asthma (AIA), as a clinical syndrome caused by aspirin, is characterized by lung inflammation and reversible bronchoconstriction. Recently, the altered trafficking and diminished airway reactivity have been implicated in allergic airway remodeling. The stromal membrane-associated protein 1-like (SMAP1L) exerts common and distinct functions in vesicle trafficking including endocytosis. The disturbance of pulmonary surfactant synthesis has been elucidated to be associated with asthma experimentally. Moreover, in alveolar type II (ATII) cells that synthesize pulmonary surfactant, alterations of clathrin-dependent endocytosis cause disturbance at the surfactant function, suggesting that SMAP1L, which directly interacts with clathrin, could be associated with asthma and related phenotypes. Objective. To verify our hypothesis that SMAP1L could play a role in the development of AIA, this study investigated associations between single-nucleotide polymorphisms (SNPs) of the SMAP1L gene and AIA. Methods. We conducted an association study between 19 SNPs of the SMAP1L gene and AIA in a total of 592 Korean subjects including 163 AIA and 429 aspirin-tolerant asthma (ATA) patients. Associations between polymorphisms of SMAP1L and AIA were analyzed with sex, smoking status, atopy, and body mass index as covariates. Results. Logistic analyses revealed that three common polymorphisms, rs2982510, rs2294752, and rs446738, were putatively associated with the increased susceptibility to AIA (p = .003, p^corr = .004, OR = 0.24, 95% CI = 0.09–0.62 for rs2982510 and rs2294752; p = .008, p^corr = .03, OR = 0.44, 95% CI = 0.24–0.80 for rs446738, in the recessive model). In addition, rs2982510 and rs2294752 were significantly associated with the fall of forced expiratory volume in 1 s (FEV₁) by aspirin provocation (p = .001, p^corr = .04 in the recessive model for both SNPs). Conclusions. Our findings suggest that SMAP1L might be a susceptible gene to AIA, providing a new strategy for the control of aspirin intolerance.

• stromal membrane-associated protein 1-like (SMAP1L)
• aspirin-intolerant asthma (AIA)
• polymorphism

Acknowledgments

This work was supported by a grant from the Korea Health 21 R&D Project (A010249); a grant (number M1-0302-00-0073) from Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (MEST) (No. 2009-0080157); an Intramural Research Grant of the Korea National Institute of Health (grant number 4800-4845-300-260-00); and a Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093822). The DNA samples were generously provided by the Soonchunhyang University, Bucheon Hospital Biobank, a member of the National Biobank of Korea, supported by the Ministry of Health, Welfare and Family Affairs, Republic of Korea.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.