Positive Association between Aspirin-Intolerant Asthma and Genetic Polymorphisms of FSIP1: a Case-Case StudyReportar como inadecuado




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BMC Pulmonary Medicine

, 10:34

First Online: 01 June 2010Received: 04 March 2010Accepted: 01 June 2010

Abstract

BackgroundAspirin-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 α 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.

ObjectivesAim 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.

MethodsWe 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.

ResultsInitially, 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.

ConclusionAlthough 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.

AbbreviationsFSIP1Fibrous sheath-interacting protein 1

AIAAspirin-intolerant asthma

ATAAspirin-tolerant asthma

APPAmyloid beta Aβ precursor protein

ADAM33α disintegrin and metalloproteinase 33

SNPSingle nucleotide polymorphism

BMIBody mass index

FEV1Forced expiratory volume in 1 second

IgEImmuglobulin E

OACOral aspirin challenge

PAFPlatelet activating factor

htHaplotype

FVCForced Vital Capacity

PPvalue, and P Corrected P :value

LDLinkage Disequilibrium

THBS1Thrombospondin-1

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2466-10-34 contains supplementary material, which is available to authorized users.

Jason Yongha Kim, Jeong Hyun Kim contributed equally to this work.

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Autor: Jason Yongha Kim - Jeong Hyun Kim - Tae Joon Park - Joon Seol Bae - Jin Sol Lee - Charisse Flerida Pasaje - Byung Lae

Fuente: https://link.springer.com/







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