Positive Association between Aspirin-Intolerant Asthma and Genetic Polymorphisms of FSIP1: a Case-Case Study

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.

The Histological Study to Correlate the Effect of NSAIDIbuprofen on the Proportion of Epithelial Height in the Wall of Lower Respiratory Airways

“…Husain AN and Kim JY have also use gastric gavage method for drug administration in their experiments. [15,16] We preferred gastric gavage method as we could avoid the spillage of drug that could occur by oral route. Secondly we could offer a standardized drug dose of ibuprofen to mouse by taking into consideration its body weight.…”

State of the art paper Does aspirin-induced oxidative stress cause asthma exacerbation?

“…Some of them are associated with the arachidonic acid pathway (LTC4S [ 79 ], COX2 [ 80 ], cysLTR1 [ 81 ], cysLTR2 [ 82 ]), and some are related to eosinophilic inflammation (ACE [ 83 ], CCR3 [ 84 ], NLRP3 [ 85 ], TBX21 [ 86 ]) and pathogenesis of nasal polyps (TGF-β1 [ 87 ]). There are also gene polymorphisms whose relationship with AIA is not fully ascertained (FSIP1 [ 88 ], CEP68 [ 72 ], SLC22A2 [ 89 , 90 ], ADAM33 [ 91 ], EMID2 [ 92 ], TLR3 [ 93 ], ADORA1 [ 94 ], CACNG6 [ 95 ], WDR46 [ 96 ], ZNRD1 [ 97 ], KIFC1 [ 98 ], CYP2C19 [ 99 ]).…”

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“…1E). 62 In Asian populations from the International HapMap Project (http://hapmap.ncbi.nlm.nih.gov/), the FSIP1 gene is in LD with the thrombospondin-1 ( THBS1 or TSP-1 ) gene. The THBS1 gene has been implicated in a network underlying the pulmonary response to oxidative stress in asthma 63.…”