Rasmussen T E, Hallett J W, Metzger R L, Richardson D M, Harmsen W S, Goronzy J J, Weyand C M
Department of Surgery, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
J Vasc Surg. 1997 Feb;25(2):356-64. doi: 10.1016/s0741-5214(97)70358-6.
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.
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).
Distribution of HLA-DR B1 alleles was nonrandom in patients with inflammatory AAAs versus control subjects. The HLA-DR B1 alleles B115 and B10404 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.
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.
炎症性腹主动脉瘤（AAA）发生存在遗传易感性证据，17%的患者有阳性家族史。炎症性AAA与巨细胞动脉炎（GCA）之间存在家族聚集性及其他相似之处，GCA有一个映射到HLA - DR分子的遗传风险决定因素，提示遗传风险因素在炎症性AAA中起作用。本研究的目的是探讨炎症性AAA患者是否表达与6号染色体短臂上HLA - DR区域相关的疾病相关基因。
对37例手术时有炎症性AAA组织形态学表现的患者进行HLA - DR B1和HLA DQ B1等位基因多态性基因分型，并与种族匹配的健康对照者（n = 90）进行比较。
炎症性AAA患者与对照者相比，HLA - DR B1等位基因分布非随机。与对照者相比，炎症性AAA患者中HLA - DR B1等位基因B115和B10404富集（分别为47%对27%，14%对3%；p < 0.05）。对HLA - DR B1基因编码的功能相关氨基酸多态性分析显示在第70位氨基酸有相关性。炎症性AAA患者中过度表达的HLA - DR B1等位基因在第70位表达谷氨酰胺替代，而在患者队列中不占优势的等位基因表达带负电荷的天冬氨酸。患者与对照者中HLA - DQ B1等位基因分布无差异。
这些数据表明，炎症性AAA患者的遗传风险决定因素可映射到HLA - DR B1基因座。这种关联提示抗原结合在该疾病发病机制中起关键作用。
