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 of 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 AAA; however, their role in progression to the inflammatory variant is unknown. The purpose of this study was to compare HLA class II genes in patients with degenerative versus classic inflammatory AAAs and to quantify their impact as disease risk factors. Methods: Genotypes of the 12 major alleles of the HLA-DR B1 locus were determined in patients with degenerative (102) and inflammatory (40) AAAs who were compared with controls (118). Univariate and multivariate logistic regression 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 compared 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; and 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 results support the concept of a common, immune-mediated pathogenesis for AAAs that may be modulated by HLA-independent factors.