Archivio istituzionale della ricerca dell'Università degli Studi di Palermo

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Analysis of Polymorphism C558T of MAL (TIRAP) in Mediterranean Spotted Fever M. Bova1, L. Scola1, C. Colomba1, L. Vaccarino1, P. Di Gangi1, G. Santini1, G. Giammanco1, C. R. Balistreri1, D. Lio1, L. Titone Lanza Di Scalea1 1University of Palermo, Palermo, Italy Background: In our previous studies, we have demonstrated that cytokine polymorphisms, such as IFNγ +874T/A or IL-17 SNP (7488T/C), might interfere with R. Conorii infection control. In addition, we have reported that +896A/G TLR4 SNP is a component of a genetic background that might influence the clinical outcome of Boutonneuse fever (Mediterranean spotted fever, MSF). The +869G allele, that attenuates receptor signaling, was actually significantly overrepresented in symptomatic patients. Rickettsial PAMPS recognised through TLR4 and TLR2, activates the MyD-88 signaling pathway, which is involved in the transcription activation of pro-inflammatory cytokine genes. In this pathway MAL (also known as TIRAP) plays a crucial role, therefore, TIRAP polymorphisms may influence the response to the pathogen. In particular, we analyzed C558T of TIRAP that seems to attenuate TLR signaling. Methods: A total of 70 Sicilian patients affected by MSF and 230 control subjects matched for age, gender, and geographic origin were typed for TIRAP SNP (C558T) according to our laboratory procedures. Results: No significant differences between the two groups were observed; therefore, the TIRAP C558T genotypes seem not to influence the susceptibility or protection against MSF. Conclusions: The results obtained suggest that the analyzed SNP on the gene coding for MAL does not seem relevant in determining increased susceptibility for the development of MSF. Nevertheless, it is appropriate to enlarge the casuistry and the number of SNPs involved in TLR signaling pathways to better define the genetic background that modulates the immune response against R. conorii infection and the consequential clinical outcome.

Bova, M., Scola, L., Colomba, C., Vaccarino, L., Di Gangi, P., Santini, G., et al. (2014). Analysis of Polymorphism C558T of MAL (TIRAP) in Mediterranean Spotted Fever. In Verna R, D’Amico A, Santonico M, Pennazza G, Verna F, Bizzarri M: Biosensor-Based Multisensorial System: Technological Design and Clinical Applications. 2nd Joint Meeting of Pathology and Laboratory Diagnostics, 2014 September 17-20, Palermo, Italy. Am J Pathol 2014, 184(Suppl: s26 aBSTRACT HDHP1 (pp.26-26). Elsevier Health Sciences.

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