Positive association between aspirin-intolerant asthma and genetic polymorphisms of FSIP1: a case-case study.
BACKGROUND
Aspirin-intolerant asthma (AIA), which is caused by non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, causes lung inflammation and reversal bronchi reduction, leading to difficulty in breathing. Aspirin is known to affect various parts inside human body, ranging from lung to spermatogenesis. FSIP1, also known as HDS10, is a recently discovered gene that encodes fibrous sheath interacting protein 1, and is regulated by amyloid beta precursor protein (APP). Recently, it has been reported that a peptide derived from APP is cleaved by alpha disintegrin and metalloproteinase 33 (ADAM33), which is an asthma susceptibility gene. It has also been known that the FSIP1 gene is expressed in airway epithelium.


OBJECTIVE
Aim of this study is to find out whether FSIP1 polymorphisms affect the onset of AIA in Korean population, since it is known that AIA is genetically affected by various genes.


METHODS
We conducted association study between 66 single nucleotide polymorphisms (SNPs) of the FSIP1 gene and AIA in total of 592 Korean subjects including 163 AIA and 429 aspirin-tolerant asthma (ATA) patients. Associations between polymorphisms of FSIP1 and AIA were analyzed with sex, smoking status, atopy, and body mass index (BMI) as covariates.


RESULTS
Initially, 18 SNPs and 4 haplotypes showed associations with AIA. However, after correcting the data for multiple testing, only one SNP showed an association with AIA (corrected P-value = 0.03, OR = 1.63, 95% CI = 1.23-2.16), showing increased susceptibility to AIA compared with that of ATA cases. Our findings suggest that FSIP1 gene might be a susceptibility gene for aspirin intolerance in asthmatics.


CONCLUSIONS
Although our findings did not suggest that SNPs of FSIP1 had an effect on the reversibility of lung function abnormalities in AIA patients, they did show significant evidence of association between the variants in FSIP1 and AIA occurrence among asthmatics in a Korean population.
Department of Life Science, Sogang University, Seoul, Republic of Korea.
Jason Yongha
JY
Kim
Jeong Hyun
JH
Kim
Tae Joon
TJ
Park
Joon Seol
JS
Bae
Jin Sol
JS
Lee
Charisse Flerida
CF
Pasaje
Byung Lae
BL
Park
Hyun Sub
HS
Cheong
Jong-Sook
JS
Park
Sung-Woo
SW
Park
Soo-Taek
ST
Uh
Mi-Kyeong
MK
Kim
Inseon S
IS
Choi
Sang Heon
SH
Cho
Byoung Whui
BW
Choi
Choon-Sik
CS
Park
Hyoung Doo
HD
Shin
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D055963:Asthma, Aspirin-Induced / Q000208:ethnology* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea / Q000453:epidemiology; D029589:Seminal Plasma Proteins / Q000235:genetics*; D055815:Young Adult
D002352:Carrier Proteins; C552592:FSIP1 protein, human; D029589:Seminal Plasma Proteins