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Susceptibility for and Clinical Manifestations of Rheumatoid Arthritis Are Associated with Polymorphisms of the TNF-a, IL-1ß, and IL-1Ra Genes
JASMINA TRIFUNOVIC CVETKOVIC, SOLVEIG WÅLLBERG-JONSSON, BIRGITTA STEGMAYR, SOLBRITT RANTAPÄÄ-DAHLQVIST, and ANN KARI LEFVERT
ABSTRACT. Methods. Polymerase chain reaction amplification was used for analysis of TaqI restriction fragment length polymorphism (RFLP) of interleukin-1 beta (IL-1ß), variable tandem repeat polymorphism of IL-1 receptor antagonist (IL-1Ra) gene and NcoI RFLP at position -308 of tumor necrosis factor-alpha (TNF-a) gene. One hundred and fifty-four patients with RA, 42 men and 112 women, were consecutively recruited into the study through the Department of Rheumatology. Results. The allele A1 of TNF-a was more common in the patient group (p < 0.01; OR = 1.62). Patients having the genotype A1A2 seemed to develop more severe disease compared with patients with A1A1 genotype: they were younger at disease onset (p < 0.05), had a higher accumulated disease activity (p < 0.05) and worse functional class (p < 0.05). Patients with genotype A2A2 of IL-1ß had higher accumulated disease activity score than patients with A1A1 and A1A2 (p < 0.05). The allelic combination A1 IL-1ß/A2 IL-1Ra was less prevalent in RA patients who developed cardiovascular complications (p < 0.005; OR = 0.20). Conclusions. The A1 allele of TNF-a associates with RA. Genotypes A1A2 of TNF-a and A2A2 of IL-1ß are associated with more severe disease. The allelic combination A1 IL-1ß/A2 IL-1Ra is less often present in RA patients who developed cardiovascular complications. (J Rheumatol 2002;29:212-9) Key Indexing Terms:
INTERLEUKIN-1ß
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