title: A multilocus genetic study in a cohort of Italian SLE patients confirms the association with STAT4 gene and describes a new association with HCP5 gene.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE) is an autoimmune disease with complex pathogenesis in which genes and environmental factors are involved. We aimed at analyzing previously identified loci associated with SLE or with other autoimmune and/or inflammatory disorders (STAT4, IL10, IL23R, IRAK1, PSORS1C1, HCP5, MIR146a, PTPN2, ERAP1, ATG16L1, IRGM) in a sample of Italian SLE patients in order to verify or confirm their possible involvement and relative contribution in the disease.
  
  
  METHODS
  Two hundred thirty-nine consecutive SLE patients and 278 matched healthy controls were enrolled. Study protocol included complete physical examination, and clinical and laboratory data collection. Nineteen polymorphisms were genotyped by allelic discrimination assays. A case-control association study and a genotype-phenotype correlation were performed.
  
  
  RESULTS
  STAT4 was the most associated gene [P = 3 × 10(-7), OR = 2.13 (95% CI: 1.59-2.85)]. IL10 confirmed its association with SLE [rs3024505: P = 0.02, OR = 1.52 (95% CI: 1.07-2.16)]. We describe a novel significant association between HCP5 locus and SLE susceptibility [rs3099844: P = 0.01, OR = 2.06 (95% CI: 1.18-3.6)]. The genotype/phenotype correlation analysis showed several associations including a higher risk to develop pericarditis with STAT4, and an association between HCP5 rs3099844 and anti-Ro/SSA antibodies.
  
  
  CONCLUSIONS
  STAT4 and IL10 confirm their association with SLE. We found that some SNPs in PSORS1C1, ATG16L1, IL23R, PTPN2 and MIR146a genes can determine particular disease phenotypes. HCP5 rs3099844 is associated with SLE and with anti-Ro/SSA. This polymorphism has been previously found associated with cardiac manifestations of SLE, a condition related with anti-Ro/SSA antibodies. Thus, our results may provide new insights into SLE pathogenesis.
authors.affiliation: Department of Biomedicine and Prevention, Section of Genetics, School of Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ciccacci
authors.affiliation: Lupus Clinic, Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Perricone
authors.affiliation: Lupus Clinic, Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Ceccarelli
authors.affiliation: Department of Biomedicine and Prevention, Section of Genetics, School of Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Rufini
authors.affiliation: Department of Biomedicine and Prevention, Section of Genetics, School of Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Di Fusco
authors.affiliation: Lupus Clinic, Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Alessandri
authors.affiliation: Lupus Clinic, Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Spinelli
authors.affiliation: Lupus Clinic, Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Cipriano
authors.affiliation: Department of Biomedicine and Prevention, Section of Genetics, School of Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.affiliation: Lupus Clinic, Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
authors.affiliation: Department of Biomedicine and Prevention, Section of Genetics, School of Medicine, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Borgiani
authors.affiliation: Lupus Clinic, Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Conti
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D050797:STAT4 Transcription Factor / Q000235:genetics*
chemical_list: D001323:Autoantibodies; C080521:HCP5 long noncoding RNA, human; C484393:PSORS1C1 protein, human; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human