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2. Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility

Author

Diaz-Gallo, L.M., Simeon, C.P., Broen, J.C.A., Ortego-Centeno, N., Beretta, L., Vonk, M.C., Carreira, P.E., Vargas, S., Roman-Ivorra, J.A., Gonzalez-Gay, M.A., Tolosa, C., Lopez-Longo, F.J., Espinosa, G., Vicente, E.F., Hesselstrand, R., Riemekasten, G., Witte, T. de, Distler, J.H., Voskuyl, A.E., Schuerwegh, A.J., Shiels, P.G., Nordin, A., Padyukov, L., Hoffmann-Vold, A.M., Scorza, R., Lunardi, C., Airo, P., Laar, J.M. van, Hunzelmann, N., Gathof, B.S., Kreuter, A., Herrick, A., Worthington, J., Denton, C.P., Zhou, X., Arnett, F.C., Fonseca, C., Koeleman, B.P., Assasi, S., Radstake, T.R.D.J., Mayes, M.D., Martin, J., Universitat de Barcelona, Rheumatology, and CCA - Immuno-pathogenesis

Subjects
Male, Genotype, systemic sclerosis, Autoimmune diseases, Immunology, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, White People, General Biochemistry, Genetics and Molecular Biology, GWAS, IL-2/IL-21 region, Gene Frequency, Rheumatology, Scleroderma, Limited, Medizinische Fakultät, Genetic variation, Genetics, Genetic predisposition, Humans, Immunology and Allergy, Genetic Predisposition to Disease, ddc:610, Allele, Allele frequency, Scleroderma, Systemic, Malalties autoimmunitàries, Interleukins, Logistic Models, Scleroderma (Disease), Case-Control Studies, Scleroderma, Diffuse, Interleukin-2, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Female, Gene polymorphism, Esclerodèrmia, Genètica
Abstract

ObjectiveThe interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc).Patients and methodsThe case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays.ResultsWe observed evidence of association of the rs6822844 and rs907715 variants with global SSc (pc=6.6E-4 and pc=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (pc=1.7E-03 and pc=8E-4, respectively).ConclusionsThese results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.

Published
2012
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4. Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility

Author

Diaz-Gallo, L.M., Simeon, C.P., Broen, J.C.A., Ortego-Centeno, N., Beretta, L., Vonk, M.C., Carreira, P.E., Vargas, S., Roman-Ivorra, J.A., Gonzalez-Gay, M.A., Tolosa, C., Lopez-Longo, F.J., Espinosa, G., Vicente, E.F., Hesselstrand, R., Riemekasten, G., Witte, T. de, Distler, J.H., Voskuyl, A.E., Schuerwegh, A.J., Shiels, P.G., Nordin, A., Padyukov, L., Hoffmann-Vold, A.M., Scorza, R., Lunardi, C., Airo, P., Laar, J.M. van, Hunzelmann, N., Gathof, B.S., Kreuter, A., Herrick, A., Worthington, J., Denton, C.P., Zhou, X., Arnett, F.C., Fonseca, C., Koeleman, B.P., Assasi, S., Radstake, T.R.D.J., Mayes, M.D., Martin, J., et al., Diaz-Gallo, L.M., Simeon, C.P., Broen, J.C.A., Ortego-Centeno, N., Beretta, L., Vonk, M.C., Carreira, P.E., Vargas, S., Roman-Ivorra, J.A., Gonzalez-Gay, M.A., Tolosa, C., Lopez-Longo, F.J., Espinosa, G., Vicente, E.F., Hesselstrand, R., Riemekasten, G., Witte, T. de, Distler, J.H., Voskuyl, A.E., Schuerwegh, A.J., Shiels, P.G., Nordin, A., Padyukov, L., Hoffmann-Vold, A.M., Scorza, R., Lunardi, C., Airo, P., Laar, J.M. van, Hunzelmann, N., Gathof, B.S., Kreuter, A., Herrick, A., Worthington, J., Denton, C.P., Zhou, X., Arnett, F.C., Fonseca, C., Koeleman, B.P., Assasi, S., Radstake, T.R.D.J., Mayes, M.D., Martin, J., and et al.

Abstract

Item does not contain fulltext, OBJECTIVE: The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc). PATIENTS AND METHODS: The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays. RESULTS: We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (pc=6.6E-4 and pc=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (pc=1.7E-03 and pc=8E-4, respectively). CONCLUSIONS: These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.

Published
2013

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