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

BackgroundSystemic 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.Materials and methodsTwo 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.ResultsSTAT4 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.ConclusionsSTAT4 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.

Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis

“…We selected these genes on the base of our previous studies that aimed to verify the association of common variants with different autoimmune diseases susceptibility [21, 37–39]. In our previous study, STAT4 , one of the most associated gene with RA susceptibility, related with a higher susceptibility to develop RA and with ACPA positivity, while SNPs in PSORS1C1 and PTPN2 genes were differently associated with joint damage in RA, even if we did not observe an association with RA susceptibility [21].…”

Joint involvement in patients affected by systemic lupus erythematosus: application of the swollen to tender joint count ratio

“…Moreover, STR seems to be more sensitive than SLEDAI-2K in capturing joint involvement. SLE is a systemic autoimmune disease characterized by a multi-factorial etiology, a broad autoantibody profile and het- erogeneous clinical features (8)(9)(10)(11). The therapeutic strategy in SLE patients should include the control of disease activity and the prevention of chronic damage (12,13).…”

Discovering the pathogenesis of autoimmune diseases at the 9th International Congress of Autoimmunity, Nice, France, 2014

“…Thus, it could be hypothesized that the combination of the HLA locus (B27 for AS and PsA, B51 for Behçet) plus the presence of other genetic variants, including ERAP1, may be responsible for different clinical onset. It is not surprising that we failed to find any association with systemic lupus erythematosus (SLE) [4]. In this disease, the role of IL-17 is better characterized, while that of IL-23 is less clear.…”