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Analysis of 6 Genetic Loci for Disease Susceptibility in Psoriatic Arthritis GERD-MARIE ALENIUS, CAMILLA FRIBERG, STAFFAN NILSSON, JAN WAHLSTRÖM, SOLBRITT RANTAPÄÄ DAHLQVIST, and LENA SAMUELSSON
ABSTRACT. Method. One hundred twenty patients with psoriasis and defined joint disease were examined clinically, radiologically, and with laboratory-based analyses. Disease classification was based on peripheral and/or axial engagement. The tumor necrosis factor (TNF) locus, 1q21 (PSORS4), 3q21 (PSORS5), 8q24, 16q21, and the CTLA4 gene were analyzed using a total of 38 microsatellite markers and 2 single nucleotide polymorphisms (SNP). Ninety-four controls with the same ethnic background as the patients were randomly selected from the same region of Sweden. Results. An association was found with one of the markers in the TNFB locus within the HLA region (p = 0.012, pc = 0.024). Three markers at the PSORS4 locus on chromosome 1q21 and 2 markers at the 8q24 locus showed nominal p values of < 0.05. After applying the Bonferroni correction for multiple analyses these markers did not reach significance. No other marker showed significant association. In a subgroup of the patients, possible linkage disequilibrium between the TNFB123 and HLA-B antigens, B17, B27, B37, B44, and B62 was analyzed. A significant linkage (p = 0.0001) was found. Conclusion. We identified an association between psoriatic arthritis and one of the microsatellite markers within the TNFB locus at the HLA region on chromosome 6. Linkage disequilibrium between TNFB123 and certain HLA-B antigens was found. (J Rheumatol 2004;31:2230-5) Key Indexing Terms:
PSORIATIC ARTHRITIS
From the Department of Public Health and Clinical Medicine, Rheumatology, University Hospital, Umeå; and Department of Clinical Genetics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital/East and Chalmers University of Technology, Gothenburg, Sweden. Supported by grants from the Swedish Psoriasis Foundation, the Medical Faculty of the University of Umeå, and the King Gustaf Vth 80-Years Foundation. G-M. Alenius, MD, PhD, Department of Public Health and Clinical Medicine, Rheumatology, University Hospital; C. Friberg, BSc, Department of Clinical Genetics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital/East; S. Nilsson, PhD, Research Scientist, Department of Clinical Genetics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital/East and Chalmers University of Technology; J. Wahlström, MD, PhD, Professor, Department of Clinical Genetics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital/East; S. Rantapää Dahlqvist, MD, PhD, Professor, Department of Public Health and Clinical Medicine, Rheumatology, University Hospital; L. Samuelsson, PhD, Research Scientist, Department of Clinical Genetics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital/East. Dr. Alenius and Dr. Friberg contributed equally to this work. Address reprint requests to Dr. G-M. Alenius, Department of Rheumatology, University Hospital, SE-901 85 Umeå, Sweden. E-mail: gerdmarie.alenius@vll.se Submitted September 12, 2003; revision accepted June 9, 2004. |