title: TRAF3IP2 gene and systemic lupus erythematosus: association with disease susceptibility and pericarditis development.
abstract: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease. Although genetic factors confer susceptibility to the disease, only 15 % of the genetic contribution has been identified. TRAF3IP2 gene, associated with susceptibility to psoriatic arthritis and psoriasis, encodes for Act1, a negative regulator of adaptive immunity and a positive signaling adaptor in IL-17-mediated immune responses. The aim of this study was to assess the role of TRAF3IP2 gene variability in SLE susceptibility and disease phenotype in an Italian population. Two hundred thirty-nine consecutive SLE patients were enrolled. Study protocol included complete physical examination; the clinical and laboratory data were collected. Two hundred seventy-eight age- and ethnicity-matched healthy subjects served as controls. TRAF3IP2 polymorphisms (rs33980500, rs13190932, and rs13193677) were analyzed in both cases and controls. Genotype analysis was performed by allelic discrimination assays. A case-control association study and a genotype-phenotype correlation were performed. The rs33980500 and rs13193677 resulted significantly associated with SLE susceptibility (P = 0.021, odds ratio (OR) = 1.71, and P = 0.046, OR = 1.73, respectively). All three TRAF3IP2 single nucleotide polymorphisms resulted associated with the development of pericarditis; in particular, rs33980500 showed the strongest association (P = 0.002, OR 2.59). This association was further highlighted by binary logistic regression analysis. In conclusion, our data show for the first time the contribution of TRAF3IP2 genetic variability in SLE susceptibility, providing further suggestions that common variation in genes that function in the adaptive and innate arms of the immune system are important in establishing SLE risk. Our study also shows that this gene may affect disease phenotype and, particularly, the occurrence of pericarditis.
authors.affiliation: Lupus Clinic, Reumatologia, Dipartimento di Clinica e Terapia Medica, Sapienza Università di Roma, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Perricone
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ciccacci
authors.forename: Fulvia
authors.initials: F
authors.lastname: Ceccarelli
authors.forename: Davide
authors.initials: D
authors.lastname: Di Fusco
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Spinelli
authors.forename: Enrica
authors.initials: E
authors.lastname: Cipriano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Conti
authors.forename: Paola
authors.initials: P
authors.lastname: Borgiani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010493:Pericarditis / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins