Department of Clinical Sciences, Lund University, Malmö University Hospital, Malmö, Sweden.
J Intern Med. 2010 Jul;268(1):50-8. doi: 10.1111/j.1365-2796.2009.02209.x. Epub 2009 Dec 14.
Human leucocyte antigens (HLAs) are polymorphic molecules involved in antigen presentation. Associations between HLA type and autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis, are well established but the potential association of genetic variation affecting antigen presentation with cardiovascular disease has not been systematically investigated in large cohorts. The importance of such studies is stressed by recent experimental findings of an involvement of autoimmunity in the atherosclerotic disease process.
An SSP-PCR method was used for HLA genotyping to determine associations of HLA-DRB1, -DQA1 and -DQB1 with cardiovascular disease in a population-based cohort of 1188 acute myocardial infarction (AMI) patients and 1191 matched healthy controls. The HLA-DRB10101 allele, as well as the HLA-DRB10101-DQA101-DQB105 haplotype, was found to be associated with increased risk for AMI (OR 1.24; 95% CI 1.00-1.54 for both). In contrast, the DRB107 and DQA02 alleles (OR 0.78; 95% CI 0.65-0.95 for both), as well as the DRB107-DQA02-DQB*02 haplotype, conferred protection (OR 0.79; 95% CI 0.63-0.98). An HLA risk score taking each individual's both haplotypes into account was higher amongst cases (2.43 +/- 0.92 vs. 2.29 +/- 0.95, P = 0.001). The association between HLA risk score and AMI was independent of other cardiovascular risk factors assessed.
This study demonstrates that the associations between HLA-DRB1 and DQA1 loci and cardiovascular disease exists but that they are considerably weaker than those previously reported for other diseases with an established autoimmune aetiology such as type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis.
人类白细胞抗原（HLA）是参与抗原呈递的多态分子。HLA 类型与自身免疫性疾病（如 1 型糖尿病和类风湿关节炎）之间的关联已得到充分证实，但影响抗原呈递的遗传变异与心血管疾病之间的潜在关联尚未在大型队列中进行系统研究。最近的实验发现自身免疫参与动脉粥样硬化疾病过程，这强调了此类研究的重要性。
采用 SSP-PCR 方法对 1188 例急性心肌梗死（AMI）患者和 1191 例匹配的健康对照人群的 HLA-DRB1、-DQA1 和 -DQB1 进行基因分型，以确定 HLA 与心血管疾病的关联。发现 HLA-DRB10101 等位基因以及 HLA-DRB10101-DQA101-DQB105 单体型与 AMI 风险增加相关（两者的 OR 为 1.24；95%CI 为 1.00-1.54）。相比之下，DRB107 和 DQA02 等位基因（两者的 OR 为 0.78；95%CI 为 0.65-0.95）以及 DRB107-DQA02-DQB*02 单体型可提供保护（OR 为 0.79；95%CI 为 0.63-0.98）。考虑到个体的两个单体型，HLA 风险评分在病例中更高（2.43 +/- 0.92 对 2.29 +/- 0.95，P = 0.001）。HLA 风险评分与 AMI 的关联独立于其他评估的心血管危险因素。
本研究表明，HLA-DRB1 和 DQA1 基因座与心血管疾病之间的关联确实存在，但与 1 型糖尿病、系统性红斑狼疮和类风湿关节炎等已确立自身免疫病因的其他疾病相比，其关联要弱得多。
