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Association of Single Nucleotide Polymorphisms within Cytokine Genes with Juvenile Idiopathic Arthritis in the Czech Population
ONDREJ CINEK, PAVLA VAVRINCOVÁ, ILJA STRIZ, PAVEL DREVÍNEK, PAVLÍNA SEDLÁKOVÁ,JAN VAVRINEC, and ANTONIJ SLAVCEV
ABSTRACT.
Methods. In a case-control study, genotypes of 130 patients with JIA (63 male, 67 female; age at onset 7.6 ± 4.4 yrs; 43 oligoarticular, 72 polyarticular, 15 systemic form) were compared to 102 healthy unrelated blood donors. Using the polymerase chain reaction technique with sequence-specific primers from the 13th IHWG workshop, we analyzed 19 single nucleotide polymorphisms within 12 different cytokine genes [interleukin (IL)-1a, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, transforming growth factor (TGF)-ß, interferon (IFN)-g], and related molecules (IL-1R, IL-1RA, IL-4Ra). Genotype frequencies were compared using chi-square analysis, and the significance level was corrected for the number of independent tests. Results. Significant positive association was found for the G allele of the IL-4 –1098 T/G polymorphism, which was carried by 10% of cases and 25% of controls [odds ratio (OR) 0.32, 95% confidence interval (CI) 0.16–0.67, corrected p = 0.038). Also, a nonsignificant increase in the frequency of the IL-1ß +3962 C allele was detected in cases (96%) versus controls (84%) (OR 4.65, 95% CI 1.64–13.2, corrected p = 0.091). We did not replicate previously found associations with the IL-1a, IL-6, IL-10, and IL-1RA polymorphisms. Conclusion. Our study showed association with JIA for the IL-4 –1098 T/G polymorphism. It also underlines the genetic contribution of IL-1 polymorphisms to the pathogenesis of JIA, as another polymorphism within the IL-1ß may influence the risk of the disease. (J Rheumatol 2004;31:1206-10) Key Indexing Terms:
JUVENILE IDIOPATHIC ARTHRITIS
From the Department of Paediatrics, Motol University Hospital, and the Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Supported in part by the Lvice Foundation, Ministry of Education Grant 111300003, and Ministry of Health Grant 6843-3. O. Cinek, MD, PhD, Research Fellow; P. Vavrincová, MD, Rheumatology Consultant; P. Drevínek, MD, Research Fellow; P. Sedláková, Laboratory Assistant; J. Vavrinec, MD, PhD, Professor of Paediatrics, Motol University Hospital; I. Striz, MD, PhD, Professor of Immunology; A. Slavcev, MD, PhD, Head of the Laboratory of Immunogenetics, Institute for Clinical and Experimental Medicine. Address reprint requests to Dr. O. Cinek, Department of Paediatrics, Motol University Hospital, V Uvalu 84, CZ-150 06, The Czech Republic. E-mail: Ondrej.Cinek@Lfmotol.cuni.cz Submitted April 11, 2003; revision accepted December 5, 2003.
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