title: 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.
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, H-1089 Budapest, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Ungvári
authors.forename: Eva
authors.initials: E
authors.lastname: Hadadi
authors.forename: Viktor
authors.initials: V
authors.lastname: Virág
authors.forename: András
authors.initials: A
authors.lastname: Bikov
authors.forename: Adrienne
authors.initials: A
authors.lastname: Nagy
authors.forename: Agnes F
authors.initials: AF
authors.lastname: Semsei
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gálffy
authors.forename: Lilla
authors.initials: L
authors.lastname: Tamási
authors.forename: Ildikó
authors.initials: I
authors.lastname: Horváth
authors.forename: Csaba
authors.initials: C
authors.lastname: Szalai
mesh_terms: D000328:Adult; D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D000077022:Survivin; D055815:Young Adult
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin