Tumour necrosis factor-α single nucleotide polymorphisms are not independent of HLA class I in UK Caucasians with adult onset idiopathic inflammatory myopathies
Tumour necrosis factor-α single nucleotide polymorphisms are not independent of HLA class I in UK Caucasians with adult onset idiopathic inflammatory myopathies
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DOI：
10.1093/rheumatology/kem145
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发表时间：
2007-09-01
期刊：
影响因子：
5.5
通讯作者：
Cooper, R. G.
中科院分区：
文献类型：
--
作者：
Chinoy, H.;Salway, F.;Cooper, R. G.
客观的。研究英国高加索特发性炎症性肌病 (IIM) 患者肿瘤坏死因子 a (TNF-α) 基因中的单倍型标记单核苷酸多态性 (SNP)。方法。对四个 TNF-a SNP 进行了横断面病例对照研究，将多发性肌炎 (PM) (n = 121)、皮肌炎 (DM) (n = 109) 和与其他结缔组织疾病重叠的肌炎 (CTD 重叠) (n = 73) 病例与正常受试者 (n = 177) 进行比较。对肌炎特异性/相关抗体进行分层后进行亚组分析。结果。与对照组相比，TNF-308A 等位基因与每个肌炎疾病亚组有很强的相关性[PM，比值比 (OR) 2.8，95% 置信区间 1.9-4.3； DM，或 2.5、1.6-3.8； CTD-重叠，OR 3.3，2.1-5.1]。与对照相比，TNF-308GA/AA 基因型频率显着增加（PM，OR 3.7，2.1-6.3；DM，OR 3.2，1.8-5.5' CTD 重叠，OR 5.0，2.6-9.6），表明存在显性模型。这种关联在拥有抗氨酰基转移RNA合成酶（抗合成酶）（OR 5.1，3.3-8.0）或-PM-Scl（OR 5.0，2.7-8.9）抗体的患者中最强。 -1031T 等位基因也是 DIVI（OR 2.2，1.4-3.6）、抗合成酶（OR 2.9，1.6-5.3）和 -PM-Scl（OR 5.6，1.9-6.4）抗体阳性患者的显着危险因素。在调整 HLA-B*08 后，TNF-308A 关联消失，但仍独立于 HLA-DQB1*02（两者都是构成共同祖先单倍型一部分的等位基因）。与对照组相比，HLA-B*08/TNF-308A/DRB1*03/DQA1*05/DQB1*02 单倍型是所有肌炎亚组的危险因素（OR 3.0、1.8-5.3）。结论。 TNF-308A 和 -1031T 等位基因是 IIM 的重要危险因素。在 IIM 中，TNF-308A 等位基因是共同祖先单倍型的一部分，但并不独立于 HLA-B*08。
Objective. To investigate haplotype tagging single nucleotide polymorphisms (SNPs) in the tumour necrosis factor a (TNF-alpha) gene, in UK Caucasian idiopathic inflammatory myopathy (IIM) patients.Methods. A cross-sectional, case-control study of four TNF-a SNPs was undertaken, comparing cases of polymyositis (PM) (n=121), dermatomyositis (DM) (n = 109) and myositis overlapping with other connective tissue diseases (CTD-overlap) (n = 73) with normal subjects (n = 177). Subgroup analyses were undertaken after stratifying for myositis specific/associated antibodies.Results. The TNF-308A allele demonstrated a strong association with each myositis disease subgroup vs controls [PM, odds ratio (OR) 2.8, 95% confidence interval 1.9-4.3; DM, OR 2.5, 1.6-3.8; CTD-overlap, OR 3.3, 2.1-5.1]. The TNF-308GA/AA genotype frequency was significantly increased vs controls (PM, OR 3.7, 2.1-6.3; DM, OR 3.2,1.8-5.5' CTD-overlap, OR 5.0, 2.6-9.6) suggesting a dominant model. The association was strongest in patients possessing anti-aminoacyl transfer RNA synthetase (anti-synthetase) (OR 5.1, 3.3-8.0) or -PM-Scl (OR 5.0, 2.7-8.9) antibodies. The -1031T allele was also a significant risk factor in DIVI (OR 2.2, 1.4-3.6), anti-synthetase (OR 2.9, 1.6-5.3) and -PM-Scl (OR 5.6, 1.9-6.4) antibody positive patients. The TNF-308A association was lost after adjusting for HLA-B*08, but remained independent of HLA-DQB1*02 (both are alleles forming part of the common ancestral haplotype). The HLA-B*08/TNF-308A/DRB1*03/ DQA1 *05/DQB1 *02 haplotype was a risk factor in all myositis subgroups vs controls (OR 3.0, 1.8-5.3).Conclusions. TNF-308A and -1031T alleles are significant risk factors in the IIMs. In the IIMs, the TNF-308A allele is part of the common ancestral haplotype, but is not independent of HLA-B*08.