P255	A combination of DRB1 and TNF genetic markers is strongly associated with aortoiliac atherosclerotic occlusive disease.
E.Blanco, A.Mas, G.Moñux, E.Urcelay, F.Serrano, E.de la Concha, A.Martinez
San Carlos Hospital, Madrid, ES.

Introduction: Atherosclerotic occlusive disease (AOD) is a clinical manifestation of peripheral arteriosclerosis, whose inflammatory etiology is influenced by both environmental and genetic factors. Atherosclerosis has been associated with some HLA-DRB1 alleles, stressing its relationship to autoimmune disorders. Conversely, in Rheumatoid Arthritis patients, the DRB1*0404 allele is associated with endothelial dysfunction. Our objective was to assess the role of HLA alleles in the susceptibility to AOD; a combined study of the TNF locus was also performed. Materials and Methods: 107 AOD patients and 519 healthy controls from the Madrid region were included. DRB1 typing and DRB1*04 subtyping was done by PCR amplification followed by hybridisation with specific oligonucleotides. TNFab microsatellites were studied with PCR and capillary electrophoresis. Data were analysed using Chi-square or Fisher exact test and haplotypic frequencies were estimated with the expectation-maximisation algorithm. Results: The DRB1*0404 was found to be associated with AOD (OR=2.36; p=0.037). None of the TNF alleles was associated overall. However, among DRB1*0404 individuals, TNFa11b4 was much more frequent in patients than in controls (OR=16.0; p=0.007). The combined appearance of TNFa11b4 and DRB1*0404 was much more frequent in patients than in controls (OR=5.90; p=0.0013), a result enhanced further by haplotypic estimates (OR=10.0; p=0.00017). Conclusion: The HLA modulates the risk of suffering from AOD. More specifically, our data suggest that an extended haplotype encompassing DRB1*0404 and TNFa11b4 carries an inflammatory genetic factor conferring susceptibility to AOD.

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