Genetic similarity in inflammatory and degenerative abdominal aortic aneurysms: A study of human leukocyte antigen class II disease risk genes

Purpose: Clinically, abdominal aortic aneurysms (AAAs) display a spectrum o f inflammation that extends from apparently noninflamed (degenerative) AAAs to the classic inflammatory variant. Genes encoded in the human leukocyte antigen (HLA) region are important in the development of both variants of A AA; however, their role in progression to the inflammatory variant is unkno wn. The purpose of this study was to compare HLA class II genes in patients with degenerative versus classic inflammatory AAAs and to quantify their i mpact as disease risk factors. Methods: Genotypes of the 12 major alleles of the HLA-DR B1 locus were dete rmined in patients with degenerative (102) and inflammatory (40) AAAs who w ere compared with controls (118). Univariate and multivariate logistic regr ession analyses were used to determine allele distributions and to quantify disease risk. Results: Distribution of the HLA-DR B1 alleles was nonrandom and similar in both degenerative and inflammatory AAA groups compared with controls. The B1*02 and B1*04 alleles were enhanced in both degenerative (39.2% vs 25.4%, P = .03; and 35.3% vs 24.6%, P = .08 respectively) and inflammatory (47.5% vs 25.4%, P = .01; and 32.5% vs 24.6%, P = .09, respectively) AAAs compare d with controls. The B1*02 and B1*04 alleles were associated with risk for both degenerative (odds ratio [OR] 2.2; 95% CI, 1.2-4.0; and OR 2.0; 95% CI , 1.1-3.7, respectively) and inflammatory AAAs (OR 3.7; 95% CI, 1.8-8.6; an d OR 2.5; 95% CI, 1.1-6.1). Conclusion: This study demonstrates that identical HLA alleles function as genetic risk factors for both inflammatory and degenerative AAAs. These res ults support the concept of a common, immune-mediated pathogenesis for AAAs that may be modulated by HLA-independent factors.