STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects
Sjögren’s syndrome (SS) is a chronic autoimmune condition characterized by autoantibody production, sicca syndrome, and periepithelial lymphocytic lesions in target tissues. A predisposing genetic background is likely, and, to date, several polymorphisms in non-HLA genes have been explored with inte...
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/7682827 |
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| author | Serena Colafrancesco Cinzia Ciccacci Roberta Priori Andrea Latini Giovanna Picarelli Francesca Arienzo Giuseppe Novelli Guido Valesini Carlo Perricone Paola Borgiani |
| author_facet | Serena Colafrancesco Cinzia Ciccacci Roberta Priori Andrea Latini Giovanna Picarelli Francesca Arienzo Giuseppe Novelli Guido Valesini Carlo Perricone Paola Borgiani |
| author_sort | Serena Colafrancesco |
| collection | DOAJ |
| description | Sjögren’s syndrome (SS) is a chronic autoimmune condition characterized by autoantibody production, sicca syndrome, and periepithelial lymphocytic lesions in target tissues. A predisposing genetic background is likely, and, to date, several polymorphisms in non-HLA genes have been explored with interesting results. We investigated the association between the STAT4, TRAF3IP2, HCP5, and IL10 polymorphisms and SS susceptibility and their possible role in the modulation of clinical and laboratory features. 195 consecutive patients with SS were enrolled and clinical and laboratory data were collected. 248 age- and sex-matched healthy subjects were used as controls. Genotyping was performed by allelic discrimination assays. A case-control association study and a phenotype-genotype correlation analysis were performed. A genetic risk profile was developed considering the risk alleles. Both the variant alleles of rs7574865 in the STAT4 gene and rs3099844 in the HCP5 gene were significantly more prevalent in patients than in controls (OR=1.91 and OR=2.44, respectively). The variant allele of rs3024505 of IL10 resulted to be a susceptibility allele (OR=1.52), while the variant allele of rs1800872 seemed to confer a protective effect for the development of the disease (OR=0.65). A risk genetic profile showed a higher probability to develop the disease in subjects with at least three risk alleles; subjects with 4 risk alleles were not observed in the controls. HCP5 rs3099844 was associated with anti-SSA (P=0.006, OR=3.07) and anti-SSB (P=0.005, OR=2.66) antibodies, severity of focus score (P=0.03, OR=12), and lymphoma development (P=0.002, OR=7.23). Patients carrying the STAT4 rs7574965 variant allele had a higher risk of monoclonal component and leukopenia (P=0.002, OR=7.6; P=0.048, OR=2.01, respectively). We confirmed the association of SS with the STAT4 and IL10 genes and we describe a novel association with HCP5. In particular, we describe an association of this specific SNP of HCP5 not only with disease development but also with autoantibody production and focus score suggesting a potential contribution of this variant to a more severe phenotype. |
| format | Article |
| id | doaj-art-68c34e221c7a44998cd2156d2e6b8ff8 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-68c34e221c7a44998cd2156d2e6b8ff82025-02-03T05:43:44ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/76828277682827STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical AspectsSerena Colafrancesco0Cinzia Ciccacci1Roberta Priori2Andrea Latini3Giovanna Picarelli4Francesca Arienzo5Giuseppe Novelli6Guido Valesini7Carlo Perricone8Paola Borgiani9UOC Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, ItalyDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, ItalyUOC Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, ItalyDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, ItalyUOC Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, ItalyUOC Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, ItalyDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, ItalyUOC Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, ItalyUOC Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, ItalyDepartment of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, ItalySjögren’s syndrome (SS) is a chronic autoimmune condition characterized by autoantibody production, sicca syndrome, and periepithelial lymphocytic lesions in target tissues. A predisposing genetic background is likely, and, to date, several polymorphisms in non-HLA genes have been explored with interesting results. We investigated the association between the STAT4, TRAF3IP2, HCP5, and IL10 polymorphisms and SS susceptibility and their possible role in the modulation of clinical and laboratory features. 195 consecutive patients with SS were enrolled and clinical and laboratory data were collected. 248 age- and sex-matched healthy subjects were used as controls. Genotyping was performed by allelic discrimination assays. A case-control association study and a phenotype-genotype correlation analysis were performed. A genetic risk profile was developed considering the risk alleles. Both the variant alleles of rs7574865 in the STAT4 gene and rs3099844 in the HCP5 gene were significantly more prevalent in patients than in controls (OR=1.91 and OR=2.44, respectively). The variant allele of rs3024505 of IL10 resulted to be a susceptibility allele (OR=1.52), while the variant allele of rs1800872 seemed to confer a protective effect for the development of the disease (OR=0.65). A risk genetic profile showed a higher probability to develop the disease in subjects with at least three risk alleles; subjects with 4 risk alleles were not observed in the controls. HCP5 rs3099844 was associated with anti-SSA (P=0.006, OR=3.07) and anti-SSB (P=0.005, OR=2.66) antibodies, severity of focus score (P=0.03, OR=12), and lymphoma development (P=0.002, OR=7.23). Patients carrying the STAT4 rs7574965 variant allele had a higher risk of monoclonal component and leukopenia (P=0.002, OR=7.6; P=0.048, OR=2.01, respectively). We confirmed the association of SS with the STAT4 and IL10 genes and we describe a novel association with HCP5. In particular, we describe an association of this specific SNP of HCP5 not only with disease development but also with autoantibody production and focus score suggesting a potential contribution of this variant to a more severe phenotype.http://dx.doi.org/10.1155/2019/7682827 |
| spellingShingle | Serena Colafrancesco Cinzia Ciccacci Roberta Priori Andrea Latini Giovanna Picarelli Francesca Arienzo Giuseppe Novelli Guido Valesini Carlo Perricone Paola Borgiani STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects Journal of Immunology Research |
| title | STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects |
| title_full | STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects |
| title_fullStr | STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects |
| title_full_unstemmed | STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects |
| title_short | STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects |
| title_sort | stat4 traf3ip2 il10 and hcp5 polymorphisms in sjogren s syndrome association with disease susceptibility and clinical aspects |
| url | http://dx.doi.org/10.1155/2019/7682827 |
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