title: Cytokine gene considerations in giant cell arteritis: IL10 promoter polymorphisms and a review of the literature.
abstract: 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.
authors.affiliation: Division of Rheumatology, Hospital Universitario Marqués de Valdecilla-IFIMAV, Facultad de Medicina, Universidad de Cantabria, Avda. Valdecilla s/n, 39008, Santander, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Alvarez-Rodriguez
authors.forename: Marcos
authors.initials: M
authors.lastname: Lopez-Hoyos
authors.forename: Eugenio
authors.initials: E
authors.lastname: Carrasco-Marín
authors.forename: Gaurav
authors.initials: G
authors.lastname: Tripathi
authors.forename: Pedro
authors.initials: P
authors.lastname: Muñoz Cacho
authors.forename: Cristina
authors.initials: C
authors.lastname: Mata
authors.forename: Jaime
authors.initials: J
authors.lastname: Calvo-Alen
authors.forename: Maite
authors.initials: M
authors.lastname: Garcia-Unzueta
authors.forename: Elena
authors.initials: E
authors.lastname: Aurrecoechea
authors.forename: Victor Manuel
authors.initials: VM
authors.lastname: Martinez-Taboada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D013700:Giant Cell Arteritis / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D016753:Interleukin-10