Putative association of SMAPIL polymorphisms with risk of aspirin intolerance in asthmatics.
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.
Kim
Jason Yongha
JY
Department of Life Science, Sogang University, Shinsu-dong, Seoul, Republic of Korea.
Kim
Jeong-Hyun
JH
Park
Byng-Lae
BL
Cheong
Hyun Sub
HS
Park
Jong Sook
JS
Jang
An Soo
AS
Uh
Soo-Taek
ST
Choi
Jae-Sung
JS
Kim
Yong-Hoon
YH
Kim
Mi-Kyeong
MK
Choi
Inseon S
IS
Cho
Sang Heon
SH
Choi
Byoung Whui
BW
Park
Choon-Sik
CS
Shin
Hyoung Doo
HD
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D055963:Asthma, Aspirin-Induced / Q000235:genetics*; D015992:Body Mass Index; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012737:Sex Factors; D012907:Smoking; D055815:Young Adult
D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; C553893:SMAP2 protein, human