Implication of BIRC5 in asthma pathogenesis

Abstract

In the last few years, it has been recognized that the unbalanced regulation of survival and apoptosis of bronchial inflammatory cells is a key component in the development of asthma. Baculoviral IAP repeat containing 5 (BIRC5) (also known as survivin) is an important anti-apoptotic protein that has been implicated in many cancer types, and recent studies provide evidence for its role in controlling inflammatory disorders as well. Our aim was to investigate at both genetic and transcriptional levels if BIRC5 has an impact on asthma development. We found that induced sputum samples of patients with bronchial asthma contained elevated levels of BIRC5 mRNA compared with healthy subjects and its level was in correlation with sputum eosinophil percentages. Furthermore, in a case-control study examining single nucleotide polymorphisms (SNPs) in the BIRC5 regulatory regions, the minor alleles of rs8073903 and rs8073069 were found to be significantly associated with asthma and especially non-allergic asthma phenotypes, which associations were more prominent among women. Two marker haplotype analyses further strengthen the impact of these two polymorphisms on both asthma and non-allergic asthma. In the female cohort, rs1508147 was also significantly associated with increased risk of non-allergic asthma. Additionally, with linear regression analysis, we showed that rs9904341 was significantly correlated with both absolute and relative serum eosinophil levels. In conclusion, our results suggest that possibly by inhibition of the eosinophil apoptosis, BIRC5 might be an important regulator of the asthmatic processes and we provide some evidence that its effect might be affected by SNPs located in the gene regulatory regions.

The role of eosinophils and basophils in allergic diseases considering genetic findings

“…The last study [32] investigated association between Baculoviral IAP repeat containing 5 (BIRC5, also called survivin), a member of the inhibitor of apoptosis protein family and blood eosinophils in a case-control study (307 asthma /344 control Hungarian subjects). The authors found that individuals homozygous for the wild-type allele of rs9904341 had elevated eosinophil levels compared to those carrying either one or two copy of the rare allele.…”

Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy

“…Furthermore, genetic variations in the BIRC5 gene (also known as survivin), which is one of the target genes of YAP1 (Fig. 1), influenced the susceptibility to the disease 16. In addition, the sputum mRNA level of FRMD6 was significantly lower, while that of BIRC5 was higher in asthmatic patients than in healthy controls 1516…”

Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations

“…Their detailed characteristics were previously described by Ungvári et al12 The asthmatic patients had mild to moderate stable asthma, with neither other lung diseases nor lower respiratory tract infection. Patients were required to have FEV1 of greater than 70% of predicted, baseline methacholine PC20 (the provocative concentration of methacholine causing a 20% fall in FEV1) of less than 16 mg/mL.…”

“…Sputum induction was carried out as previously described by Ungvári et al12,16 RNA was isolated with Qiagen Mini Rneasy Kit (Qiagen, MD USA) and transcribed to cDNA with High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Foster City, CA, USA). Real-time quantitative PCR was performed for the selected genes using the ABI 7900HT Fast Real-Time PCR System (Applied Biosystems, Foster City, CA, USA).…”