Cytokine Gene Considerations in Giant Cell Arteritis: IL10 Promoter Polymorphisms and a Review of the Literature
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Polymorphisms of cytokine genes have been investigated as susceptibility markers of giant cell arteritis (GCA). Here, we have reviewed the evidence to date and especially addressed the functional consequences of IL10 (−592C/A and −1082A/G) gene polymorphisms and their association with susceptibility to and disease phenotype in GCA. A total number of 71 patients with GCA and 124 age-matched controls were genotyped using allele-specific primers and restriction fragment length polymorphism analysis. As previous studies in GCA showed inconsistent results, a meta-analysis of the existing studies was also conducted by using both fixed and random-effects models. The levels of circulating IL10 and the production of IL10 by peripheral blood mononuclear cells after in vitro stimulation were studied by Cytometric Bead Array. Data showed no significant differences in genotype or allele frequency distribution between patients and controls. The clinical characteristics and prognosis of these patients were also unrelated to the presence of these polymorphisms. However, the meta-analysis found a significant association of IL10 −592C/A polymorphism with susceptibility to GCA (odds ratio 2.205 (95 % confidence interval 1.074–4.524); p = 0.031). In both patients and age-matched controls, no differences in circulating IL10 levels or IL10 production were observed depending on the genotypes of the IL10 gene. In conclusion, although our cohort results do not support the impact of IL10 variants in susceptibility or clinical phenotype of GCA patients, the meta-analysis revealed a significant association of −592C/A polymorphism with susceptibility to GCA. In this population, no functional association was found between IL10 gene variants and IL10 production.
KeywordsCytokines Giant cell arteritis Interleukin 10 IL10 gene polymorphism Meta-analysis
This work was supported by grants from Fundación Marqués de Valdecilla—IFIMAV and Fondo de Investigación Sanitaria (PI050475 and PI080098). LA-R and GT were supported by a grant for Research Aid from Fundación Marqués de Valdecilla—IFIMAV. We are especially grateful to Iñaki Beares and Marta Gonzalez (supported by Fundación Marqués de Valdecilla—IFIMAV) and Carolina Santa Cruz (supported by a grant for Research Aid from Schering-Ploug, Spain) for their helpful technical assistance. We would like to thank all the patients and controls included in the present study.
Conflict of Interest
No financial interest has been disclosed by any of the authors.
- 2.Martínez-Taboada VM, Goronzy JJ, Weyand CM (1994) Conceptos actuales sobre la patogenia de la arteritis de células gigantes. Rev Esp Rheumatol 2:293–299Google Scholar
- 6.Salvarani C, Casali B, Farnetti E et al (2005) Interleukin-6 promoter polymorphism at position −174 in giant cell arteritis. J Rheumatol 2:2173–2177Google Scholar
- 13.Enjuanes A, Benavente Y, Hernández-Rodríguez J et al (2012) Association of NOS2 and potential effect of VEGF, IL6, CCL2 and IL1RN polymorphisms and haplotypes on susceptibility to GCA—a simultaneous study of 130 potentially functional SNPs in 14 candidate genes. Rheumatology 51:841–851PubMedCrossRefGoogle Scholar
- 16.Alvarez-Rodríguez L, López-Hoyos M, Carrasco-Marín E et al (2012) Analysis of the rs20541 (R130Q) polymorphism in the IL-13 gene in patients with elderly-associated chronic inflammatory diseases. Rheumatol Clin 8:321–327Google Scholar
- 34.Armona J, Rodríguez-Valverde V, González-Gay MA et al (1995) Arteritis de células gigantes. Estudio de 191 pacientes. Med Clin (Barc) 105:734–737Google Scholar
- 40.Borenstein M, Hedges LV, Higgins JPT, Rothstein HR (2005) Comprehensive meta analysis version 2. Biostat, EnglewoodGoogle Scholar