Please cite this article in press as: Zupin, L., et al., NLRC5 polymorphism is associated with susceptibility to chronic periodontitis. Immunobiology (2017), http://dx.doi.org/10.1016/j.imbio.2017.01.001 ARTICLE IN PRESS G Model IMBIO-51597; No. of Pages 5 Immunobiology xxx (2017) xxx–xxx Contents lists available at ScienceDirect Immunobiology journal homepage: www.elsevier.com/locate/imbio NLRC5 polymorphism is associated with susceptibility to chronic periodontitis Luisa Zupin a,∗ , Chiara Ottavia Navarra a , Antonietta Robino b , Lorenzo Bevilacqua a , Roberto Di Lenarda a , Paolo Gasparini a,c , Sergio Crovella a,b a Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy b Institute for Maternal and Child Health − IRCCS “Burlo Garofolo”, Trieste, Italy c Division Experimental Genetics, Sidra, Doha, Qatar a r t i c l e i n f o Article history: Received 9 November 2016 Received in revised form 9 January 2017 Accepted 9 January 2017 Available online xxx Keywords: Inflammasomes NLRC5 Periodontitis a b s t r a c t Periodontitis is a chronic oral pathology caused by impaired immune response against oral bacteria resulting in tissue inflammation and damage. Among the members of innate immune response, the first line of defence against pathogens, inflammasomes are macro-molecular protein complexes that can be activated by different stimuli, comprised bacteria infections. Different proteins are involved in inflammasoma formation; the most important are molecules belonging from the family of nucleotide- binding and oligomerization domain (NOD)-like receptors (NLRs). In this study, polymorphisms within 20 NLRs related genes were analysed in order to investigate their possible association with periodontitis susceptibility in a population from North-East Italy. One polymorphism, namely rs289723, in NLRC5 gene resulted associated with chronic slight and chronic localized periodontitis susceptibility, specifically A/A genotype was correlated with increased risk of disease development. Our study, for the first time, identified the possible involvement of a polymorphism within NLRC5 gene as a possible biomarker for periodontitis condition susceptibility among Italian individuals from genetic isolates. © 2017 Elsevier GmbH. All rights reserved. 1. Introduction Periodontitis is an oral world-wide medical problem character- ized by a progressive destruction of dental supporting tissues and it is one of the major causes of tooth loss in adults (Pihlstrom et al., 2005). In fact, in its chronic form, periodontitis is one of the most common inflammatory diseases that presents a prevalence of about 37% in Europe (35–44 years old) (Sheiham and Netuveli, 2002) and of 35–40% in North Italy (20–75 years old) (Aimetti et al., 2015). Many factors are involved in the periodontal disease development, such as oral hygiene habits, smoking, diabetes, stress, medication and nutrition (Van Dyke and Sheilesh, 2005), however individu- als are not susceptible in an equal manner to this disease (Van der Velden et al., 2006). Initially a gingival inflammatory and immune response activates against microbial plaque accumulation: the majority of infections ∗ Corresponding author at: Department of Medicine, Surgery and Health Sciences, University of Trieste, Via dell’Istria 65/1, 34137, Trieste, Italy. E-mail address: luisa.zupin@burlo.trieste.it (L. Zupin). are generally resolved, however when innate immunity, the host first line of defence, fails, the adaptive response is activated thus leading to a chronic status of inflammation against pathogens with the destruction of homeostasis between host and bacteria resulting in tissue damage (Ebersole et al., 2013), teeth loose, pain, loss of connective tissue and destruction of alveolar bone (Pihlstrom et al., 2005). Among the innate immunity members, the family of nucleotide- binding and oligomerization domain (NOD)-like receptors (NLRs) has a pivotal role against pathogens. They are pattern recognition receptors able to recognize microbial and danger offence, providing immediate response and mediating the adaptive immune system reaction (Medzhitov, 2009). The molecules of NLRs family are characterized by the presence of conserved domains at the amino-terminal for the protein-protein interactions (caspase-recruitment domain (CARD)- pyrin-domain (PYD) and baculovirus inhibitor of apoptosis repeat (BIR) domain), a central nucleotide binding oligomerization domain (NOD) and leucine rich repeats at the carboxy-terminal for the microbial sensing (Inohara et al., 2005). Different stimuli could activate the proteins and lead to the assembly of a macro-molecular http://dx.doi.org/10.1016/j.imbio.2017.01.001 0171-2985/© 2017 Elsevier GmbH. All rights reserved.