PURPOSE: Evidence of a genetic predisposition to the development of inflammatory abdominal aortic aneurysms (AAAs) exists as a positive family history in 17% of patients. Familial clustering and other similarities between inflammatory AAAs and giant cell arteritis (GCA), which possesses a genetic risk determinant mapped to the HLA-DR molecule, suggest a role of genetic risk factors in inflammatory AAAs. The purpose of this study was to explore whether patients with inflammatory AAAs express disease-relevant genes associated with the HLA-DR region on the short arm of chromosome 6. METHODS: Thirty-seven patients with histomorphologic findings of inflammatory AAA at operation were genotyped for the polymorphism of the HLA-DR B1 and HLA DQ B1 alleles and compared to ethnically matched, healthy control subjects (n = 90). RESULTS: Distribution of HLA-DR B1 alleles was nonrandom in patients with inflammatory AAAs versus control subjects. The HLA-DR B1 alleles B1*15 and B1*0404 were enriched in patients with inflammatory AAAs compared with control subjects (47% versus 27%, and 14% versus 3%; p < 0.05, respectively). Analysis of functionally relevant amino acid polymorphisms encoded by the HLA-DR B1 gene showed relevance at amino acid position 70. HLA-DR B1 alleles overrepresented in patients with inflammatory AAAs express a glutamine substitution at position 70, whereas alleles disfavored in the patient cohort express a negatively charged aspartic acid. Distribution of HLA-DQ B1 alleles were indistinguishable in patients and control subjects. CONCLUSION: These data indicate that a genetic risk determinant can be mapped to the HLA-DR B1 locus in patients with inflammatory AAAs. This association suggests a critical contribution of antigen binding in the pathogenesis of this disease.
PURPOSE: Evidence of a genetic predisposition to the development of inflammatory abdominal aortic aneurysms (AAAs) exists as a positive family history in 17% of patients. Familial clustering and other similarities between inflammatory AAAs and giant cell arteritis (GCA), which possesses a genetic risk determinant mapped to the HLA-DR molecule, suggest a role of genetic risk factors in inflammatory AAAs. The purpose of this study was to explore whether patients with inflammatory AAAs express disease-relevant genes associated with the HLA-DR region on the short arm of chromosome 6. METHODS: Thirty-seven patients with histomorphologic findings of inflammatory AAA at operation were genotyped for the polymorphism of the HLA-DR B1 and HLA DQ B1 alleles and compared to ethnically matched, healthy control subjects (n = 90). RESULTS: Distribution of HLA-DR B1 alleles was nonrandom in patients with inflammatory AAAs versus control subjects. The HLA-DR B1 alleles B1*15 and B1*0404 were enriched in patients with inflammatory AAAs compared with control subjects (47% versus 27%, and 14% versus 3%; p < 0.05, respectively). Analysis of functionally relevant amino acid polymorphisms encoded by the HLA-DR B1 gene showed relevance at amino acid position 70. HLA-DR B1 alleles overrepresented in patients with inflammatory AAAs express a glutamine substitution at position 70, whereas alleles disfavored in the patient cohort express a negatively charged aspartic acid. Distribution of HLA-DQ B1 alleles were indistinguishable in patients and control subjects. CONCLUSION: These data indicate that a genetic risk determinant can be mapped to the HLA-DR B1 locus in patients with inflammatory AAAs. This association suggests a critical contribution of antigen binding in the pathogenesis of this disease.
Authors: Song Lu; John V White; Wan Lu Lin; Xiaoying Zhang; Charalambos Solomides; Kyle Evans; Nectaria Ntaoula; Ifeyinwa Nwaneshiudu; John Gaughan; Dimitri S Monos; Emilia L Oleszak; Chris D Platsoucas Journal: J Immunol Date: 2014-04-21 Impact factor: 5.422
Authors: H H S Kharagjitsing; J van Vooren; E G Brilman; T R Hendriksz; T van Gelder; E F H van Bommel Journal: Rheumatol Int Date: 2021-11-25 Impact factor: 2.631
Authors: Teodora Radonic; Piet de Witte; Maarten Groenink; Vivian de Waard; Rene Lutter; Marco van Eijk; Marnix Jansen; Janneke Timmermans; Marlies Kempers; Arthur J Scholte; Yvonne Hilhorst-Hofstee; Maarten P van den Berg; J Peter van Tintelen; Gerard Pals; Marieke J H Baars; Barbara J M Mulder; Aeilko H Zwinderman Journal: PLoS One Date: 2012-03-30 Impact factor: 3.240
Authors: Toru Ogata; Lucie Gregoire; Katrina A B Goddard; Magdalena Skunca; Gerard Tromp; Wayne D Lancaster; Antonio R Parrado; Qing Lu; Hidenori Shibamura; Natzi Sakalihasan; Raymond Limet; Gerald L MacKean; Claudette Arthur; Taijiro Sueda; Helena Kuivaniemi Journal: BMC Med Genet Date: 2006-07-31 Impact factor: 2.103