HLA CLASS-II (DR AND DQ) ANTIGEN ASSOCIATIONS IN IDIOPATHIC DILATED CARDIOMYOPATHY - VALIDATION-STUDY AND METAANALYSIS OF PUBLISHED HLA ASSOCIATION STUDIES
HLA CLASS-II (DR AND DQ) ANTIGEN ASSOCIATIONS IN IDIOPATHIC DILATED CARDIOMYOPATHY - VALIDATION-STUDY AND METAANALYSIS OF PUBLISHED HLA ASSOCIATION STUDIES
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DOI：
10.1161/01.cir.83.2.515
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发表时间：
1991-02-01
期刊：
影响因子：
37.8
通讯作者：
ANDERSON, JL
中科院分区：
文献类型：
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作者：
CARLQUIST, JF;MENLOVE, RL;ANDERSON, JL
我们先前在一项初步研究中报道了特发性扩张型心肌病（IDC）患者和健康对照者之间HLA-DR 4和HLA-DRw 6抗原频率的差异。为了证实这些发现，我们进行了一项独立的研究，一个前瞻性的假设，关于DR 4和DRw 6的频率;分型的第二个家庭的第二类抗原（HLA-DQ），因为接近的DQ位点的DR位点和一些DR和DQ等位基因之间的强连锁不平衡。比较IDC患者（n = 41）和健康血库对照（n = 53）的新的连续系列，我们证实患者中DR 4抗原频率增加（49%对21%，p < 0.005）。还注意到患者中DRw 6表达降低的趋势（10%的患者对23%的对照）。与对照组相比，HLA-DQw 4在患者中显著升高（27%对6%，p < 0.005;相对危险度，6.1;病因分数，0.22）。我们在41名高加索IDC患者中的5名（12%）和53名对照中的0名（p < 0.007）中鉴定了组合的DR 4-DQw 4单倍型。初步研究和验证研究之间特异性抗原频率的比较未显示显著差异;因此，对两项研究的数据进行了合并检查。在联合研究中，DR 4升高（51% vs 27%，对照组，p < 0.001），DRw 6降低（9% vs 24%，对照组，p < 0.01）。DR 4的相对危险度为2.8，病因分数为0.33。在这项研究中，DR 4-DQw 4单倍型具有不确定的高疾病风险;在41例ID C病例中有26例（63%）发现DR 4、DQw 4或两种抗原的存在，而在53例对照中有14例（26%）（p < 0.001）。对探索性和验证性研究以及所有报告的比较IDC患者和对照组中HLA-DR抗原频率的研究进行荟萃分析。该综述表明，对于所有五项研究，IDC病例中HLA-DR 4的频率显著增加（总体比值比，2.06; 98%置信区间，1.61-2.65; p < 0.0001）。总之，我们已经证实了HLA-DR 4参与IDC，并提出了与DQw 4的额外关联。报告研究的荟萃分析证实，DR 4相关性可在几个不同的患者人群中重复。因此，在一部分IDC病例中，似乎存在与免疫调节基因座相关的易感遗传因素。
We previously reported antigen frequency differences for HLA-DR4 and HLA-DRw6 between idiopathic dilated cardiomyopathy (IDC) patients and healthy controls in a pilot study. To confirm these findings, we undertook an independent study with a prospective hypothesis regarding the frequencies of DR4 and DRw6; typing for a second family of class II antigens (HLA-DQ) was included because of the proximity of the DQ loci to the DR loci and the strong linkage disequilibrium between some of the DR and DQ alleles. Comparing a new consecutive series of IDC patients (n = 41) and healthy blood bank controls (n = 53), we confirmed an increase of DR4 antigen frequency in patients (49% versus 21%, p < 0.005). A trend toward decreased expression of DRw6 among patients was also noted (10% of patients versus 23% of controls). HLA-DQw4 was significantly elevated in patients compared with controls (27% versus 6%, p < 0.005; relative risk, 6.1; etiologic fraction, 0.22). We identified the combined DR4-DQw4 haplotype in five of 41 Caucasian IDC patients (12%) and none of 53 controls (p < 0.007). A comparison of specific antigen frequencies between the preliminary and validation studies did not reveal significant differences; therefore, the data from the two studies were examined in combination. For the combined studies, DR4 was elevated (51% versus 27% in controls, p < 0.001), and DRw6 was decreased (9% versus 24% in controls, p < 0.01). The relative risk for DR4 was 2.8, and the etiologic fraction was 0.33. In this study, the DR4-DQw4 haplotype bears an indeterminately high risk for disease; the presence of DR4, DQw4, or both antigens was found in 26 of 41 ID C cases (63%) compared with 14 of 53 controls (26%) (p < 0.001). Meta-analysis of the exploratory and validation studies in combination with all reported studies comparing the frequency of HLA-DR antigens in IDC patients and controls was performed. This overview indicated that for all five studies, there is a significant increase in the frequency of HLA-DR4 in cases of IDC (overall odds ratio, 2.06; 98% confidence interval, 1.61-2.65; p < 0.0001). In conclusion, we have verified HLA-DR4 involvement in IDC and suggested an additional association with DQw4. The meta-analysis of reported studies confirms that the DR4 association can be replicated in several different patient populations. Thus, in a portion of IDC cases, predisposing genetic factors linked to immunoregulatory loci appear to be present.