Polymorphisms in STAT-4, IL-10, PSORS1C1, PTPN2 and MIR146A genes are associated differently with prognostic factors in Italian patients affected by rheumatoid arthritis

C Ciccacci; P Conigliaro; C Perricone; S Rufini; P Triggianese; C Politi; G Novelli; R Perricone; P Borgiani

doi:10.1111/cei.12831

Polymorphisms in STAT-4, IL-10, PSORS1C1, PTPN2 and MIR146A genes are associated differently with prognostic factors in Italian patients affected by rheumatoid arthritis

Clin Exp Immunol. 2016 Nov;186(2):157-163. doi: 10.1111/cei.12831. Epub 2016 Aug 2.

Authors

C Ciccacci¹, P Conigliaro², C Perricone³, S Rufini¹, P Triggianese², C Politi¹, G Novelli¹, R Perricone², P Borgiani¹

Affiliations

¹ Department of Biomedicine and Prevention, Genetics Section, Rome, Italy.
² Clinic of Rheumatology, Allergology and Clinical Immunology, Department of 'Medicina Dei Sistemi', University of Rome 'Tor Vergata', Rome, Italy.
³ Reumatologia, Dipartimento Di Medicina Interna E Specialità Mediche, Sapienza Università Di Roma, Rome, Italy. carlo.perricone@gmail.com.

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease resulting in chronic inflammation of the synovium and consequent cartilage and bone erosion. RA is associated strongly with the presence of rheumatoid factor (RF), and consists of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and -negative patients. This study was designed to evaluate whether relevant single nucleotide polymorphisms (SNPs) associated with RA and other autoimmune disorders are related to RF, ACPA and clinical phenotype in a cohort of biologic drugs naive Italian RA patients; 192 RA patients and 278 age-matched healthy controls were included. Clinical and laboratory data were registered. We analysed a total of 12 single nucleotide polymorphisms (SNPs) in signal transducer and activator of transcription-4 (STAT-4), interleukin (IL)-10, psoriasis susceptibility 1 candidate 1 (PSORS1C1), protein tyrosine phosphatase, non-receptor type 2 (PTPN2), endoplasmic reticulum aminopeptidase 1 (ERAP1), tumour necrosis factor receptor-associated 3 interacting protein 2 (TRAF3IP2) and microRNA 146a (MIR146A) genes by allelic discrimination assays. Case-control association studies and genotype/phenotype correlation analyses were performed. A higher risk to develop RA was observed for rs7574865 in the STAT-4 gene, while the rs1800872 in the IL-10 gene showed a protective effect. The presence of RF was associated significantly with rs1800872 variant in IL-10, while rs2910164 in MIR146A was protective. ACPA were associated significantly with rs7574865 in STAT-4. The SNP rs2233945 in the PSORS1C1 gene was protective regarding the presence of bone erosions, while rs2542151 in PTPN2 gene was associated with joint damage. Our results confirm that polymorphisms in STAT-4 and IL-10 genes confer susceptibility to RA. For the first time, we described that SNPs in PSORS1C1, PTPN2 and MIR146A genes were associated differently with a severe disease phenotype in terms of autoantibody status and radiographic damage in an Italian RA population.

Keywords: IL-10; MIR146A; PSORS1C1; PTPN2; STAT-4; anti-citrullinated protein antibody; rheumatoid arthritis.

MeSH terms

Adult
Aged
Alleles
Arthritis, Rheumatoid / diagnosis*
Arthritis, Rheumatoid / genetics*
Case-Control Studies
Female
Genetic Association Studies
Genotype
Humans
Interleukin-10 / genetics*
Italy
Male
MicroRNAs / genetics*
Middle Aged
Odds Ratio
Phenotype
Polymorphism, Single Nucleotide
Prognosis
Protein Tyrosine Phosphatase, Non-Receptor Type 2 / genetics*
Proteins / genetics*
Risk Factors
STAT4 Transcription Factor / genetics*
Severity of Illness Index

Substances

MIRN146 microRNA, human
MicroRNAs
PSORS1C1 protein, human
Proteins
STAT4 Transcription Factor
Interleukin-10
Protein Tyrosine Phosphatase, Non-Receptor Type 2