Relationship Between Fcg Receptor and Interleukin-1 Gene Polymorphisms and Post-treatment Apical Periodontitis Jose´F. Siqueira, Jr, PhD,* Isabela N. Ro ˆc ¸as, PhD,* Jose´C. Provenzano, MSc,* Frederico K. Daibert, MSc,* Marlei G. Silva, BBS, † and Kenio C. Lima, PhD ‡ Abstract Introduction: Genetic polymorphisms have been re- ported to act as modifiers of diverse diseases and, as such, might theoretically influence the severity and response to treatment of apical periodontitis. The purpose of this study was to investigate the association of Fcg receptor and interleukin (IL)-1 gene polymorphisms with post-treatment apical periodontitis in Brazilian individuals. Methods: The study population consisted of 18 patients with post-treatment apical periodontitis and 44 individ- uals with root canal–treated teeth exhibiting healthy/heal- ing periradicular tissues (controls). Patients were typed for the following genes (alleles): FcgRIIA (R131 or H131), FcgRIIIB (NA1 or NA2), IL-1A (1 or 2), and IL-1B (1 or 2). Results: No significant statistical differences were observed for all specific genotypes and almost all allele carriage rates of the test genes as well as combinations thereof with regard to association with disease (P > .05). Actually, only 2 genetic conditions were found to be associated with post-treatment apical periodontitis: carriage of allele H131 of the FcgRIIa gene (P = .04) and a combination of this allele with allele NA2 of the FcgRIIIb gene (P < .01). Conclusions: Data from the present study suggest that some conditions associated with polymorphism of Fcg receptor genes might influence the patient’s response to endodontic treatment of teeth with apical periodontitis. (J Endod 2009;35:1186–1192) Key Words Fcgreceptor, genetic polymorphism, interleukin-1, post- treatment apical periodontitis P ost-treatment apical periodontitis is caused by microorganisms involved in persis- tent or secondary intraradicular infections or in extraradicular infections (1). Although it is widely recognized that emergence or persistence of post-treatment disease is dependent on infection (2), the possibility exists that other factors might influence the development, severity, or response to treatment of apical periodontitis lesions. These factors are usually known as disease modifiers or susceptibility/severity factors (3, 4). Interindividual variations in the response to infection might be caused by systemic conditions or the genetic background of the individual. For instance, diabetes has been demonstrated to influence the development, course, and healing of apical periodontitis (5, 6). As for the genetic influence, gene polymorphism has been demonstrated to result in differences in the expression of molecules involved in inflammation and cellular acti- vation (4). Existence of genetic polymorphisms might help explain the different courses of the same disease and the different responses to treatment in different patients (7). Genetic polymorphisms are recognized when different alleles of a gene are found in the population. In a biallelic locus, the most common allele is termed normal (N-allele or allele 1) and must occur in <99%, whereas the rarer allele (R-allele or allele 2) is present in >1% in the population. The simplest type of polymorphism involves a change from one nucleotide to another and is referred to as single nucleotide polymorphism (SNP). Occurrence of SNP within the coding region of a gene might result in production of an altered protein, which might present altered function. Occurrence of SNP within the promoter region of the gene might alter gene regulation. This might lead to reduction/ inhibition of gene expression or, conversely, overexpression of the gene (8). If the product of the polymorphic gene relates to inflammation or repair, the response might vary among individuals presenting different genotypes and carrying specific alleles. FcgR are surface receptors expressed by leukocytes for the constant (Fc) region of immunoglobulin G (IgG) (9). IgG binds bacteria or bacterial soluble products and acts as opsonins, favoring the phagocytosis via FcgR by neutrophils or internalization by antigen-presenting cells, including macrophages and B cells. T cells and natural killer cells might also become activated when their FcgRs bind IgG-opsonized bacteria (9). As a consequence of the interaction between IgG-opsonized bacteria and FcgRs on immune cells, proinflammatory cytokines can be produced and released (9). Polymor- phisms in the FcgR genes might lead to enhancement or inhibition of events mediated by FcgR and consequently might influence the susceptibility/severity to inflammatory diseases. The FcgR genes are found on chromosome 1 and encode 3 main classes of receptors: FcgRI (CD64), FcgRII (CD32), and FcgRIII (CD16). These classes are subdivided into the following subclasses: FcgRIa and b, FcgRIIa, b, and c, and FcgRIIIa and b. Polymorphism in the FcgRIIa gene (or FcgRIIA) is characterized by a G to A transition that leads to the substitution of histidine (H) (N-allele) for arginine (R) (R-allele) at amino acid position 131 of the receptor. The FcgRIIA-H131 allotype binds IgG2 immune complexes efficiently, whereas the FcgRIIA-R131 allotype cannot mediate this interaction (10). The FcgRIIIb gene (or FcgRIIIB) polymorphism is caused by 4 amino acid substitutions, which cause differences in receptor glycosylation with resulting effects on receptor affinity. Polymorphism in the FcgRIIIb gene results in the FcgRIIIB-neutrophil antigens NA1 (N-allele) or NA2 (R-allele). The FcgRIIIB-NA1 allotype promotes phagocytosis of IgG1- and IgG3-opsonized bacteria or bacterial products and binds IgG3 complexed to antigens more efficiently than FcgRIIIB-NA2 (9). Studies have found associations between polymorphisms in FcgRIIA and FcgRIIIB and the severity of periodontal diseases (11–15). From the *Department of Endodontics and Molecular Microbiology Laboratory, Esta ´cio de Sa ´ University, Rio de Janeiro, RJ; † Institute of Microbiology Prof. Paulo de Go ´ es, Federal University of Rio de Janeiro, Rio de Janeiro, RJ; and ‡ Department of Preventive Dentistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Address requests for reprints to Jose ´ F. Siqueira Jr, DDS, MSc, PhD, Faculty of Dentistry, Esta ´cio de Sa ´ University, Av. Alfredo Baltazar da Silveira, 580/cobertura, Recreio, Rio de Janeiro, RJ, Brazil 22790-710. E-mail address: jf_siqueira@ yahoo.com; siqueira@estacio.br 0099-2399/$0 - see front matter Copyright ª 2009 American Association of Endodontists. doi:10.1016/j.joen.2009.05.006 Clinical Research 1186 Siqueira Jr. et al. JOE — Volume 35, Number 9, September 2009