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Polymorphism in Promoter Region of IL10 Gene Is Associated with Rheumatoid Arthritis in Women
LEONID PADYUKOV, ANN-MARIE HYTÖNEN, MARINA SMOLNIKOVA, MIRJANA HAHN-ZORIC, NICKLAS NILSSON, LARS-ÅKE HANSON, ANDREJ TARKOWSKI, and LARS KLARESKOG
ABSTRACT. Objective. Rheumatoid arthritis (RA) is a genetically complex disease with many possible phenotypes. We investigated IL10 and TNFA gene polymorphisms in a group of Swedish women and men with RA compared with healthy individuals to estimate combinations of alleles specific for the disease. Methods. We analyzed 264 patients with RA and 286 healthy controls for biallelic single-nucleotide polymorphisms in the –308 position of the TNFA and in the –1087 position of the IL10 gene by polymerase chain reaction with restriction endonuclease mapping. Results. The frequencies of the –308 TNFA genotypes were not different in women and men with RA in comparison to the controls. In contrast, frequencies of the GG, AG, and AA –1087 IL10 genotypes were significantly different in women in the investigated groups: 26%, 58%, and 15% for RA patients and 24%, 54%, and 28% for the controls (chi-square = 8.18, p < 0.02). We confirmed this finding in a separate dataset of female patients and controls. The frequencies of the IL10 genotypes in men were similar in the patients and controls. We found no differences in the distribution of the TNFA or IL10 genotypes in relation to rheumatoid factor in the patients. Conclusion. On the basis of IL10 polymorphism, female patients with RA seem to represent a separate disease subgroup. (J Rheumatol 2004;31:422-5) Key Indexing Terms:
RHEUMATOID ARTHRITIS
From the Rheumatology Unit, Institute of Medicine, Karolinska Institutet, Stockholm, Sweden; the Departments of Clinical Immunology, Rheumatology and Inflammation Research, Sahlgrenska University Hospital, University of Göteborg, Göteborg, Sweden; and the Immunoassay Department, Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia. Dr. Padyukov was partly supported by The Swedish Institute. L. Padyukov, MD, PhD, Rheumatology Unit, Institute of Medicine, Karolinska Institutet, Department of Clinical Immunology, Sahlgrenska University Hospital, Immunoassay Department, Mechnikov Research Institute; M. Smolnikova, PhD; L. Klareskog, MD, PhD, Professor, Rheumatology Unit, Institute of Medicine, Karolinska Institutet; A-M. Hytönen, MSc; M. Hahn-Zoric, PhD; L-Å. Hanson, MD, PhD, Professor, Department of Clinical Immunology, Sahlgrenska University Hospital; N. Nilsson, MD, PhD; A. Tarkowski, MD, PhD, Professor, Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital. Address reprint requests to Dr. L. Padyukov, Unit of Rheumatology, Karolinska Institutet, CMM L8:O4, 17176, Stockholm, Sweden. E-mail: leonid.padyukov@cmm.ki.se Submitted December 3, 2002; revision accepted August 25, 2003. |