Association of tumor necrosis factor microsatellite polymorphisms with HLA-DRB1(*)04-bearing haplotypes in rheumatoid arthritis patients
Association of tumor necrosis factor microsatellite polymorphisms with HLA-DRB1(*)04-bearing haplotypes in rheumatoid arthritis patients
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DOI：
10.1002/art.1780390706
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发表时间：
1996-07-01
影响因子：
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通讯作者：
Ollier, WER
中科院分区：
文献类型：
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作者：
Hajeer, AH;Worthington, J;Ollier, WER
目标。研究1)类风湿关节炎(RA)患者肿瘤坏死因子(TNF)微卫星等位基因频率，以及2)肿瘤坏死因子微卫星与类风湿关节炎(RA)相关的人类白细胞抗原(HLA)特异性的关系，以建立扩展的HLA单倍型。对85例高加索类风湿性关节炎患者和109例健康高加索类风湿性关节炎患者进行了肿瘤坏死因子基因分型和半自动基因分型，并对56例具有特定人类白细胞抗原DRB1亚型的类风湿关节炎患者进行了肿瘤坏死因子基因分型，计算了肿瘤坏死因子与人类白细胞抗原等位基因间的连锁不平衡，建立了扩展的单倍型。与对照组相比，RA患者的TNFa6等位基因频率显著增加(P=0.0019，优势比[OR]2.5，95%可信区间[95%CI]1.3~4.6)，在HLADRB1*0401纯合子患者中增加更为明显(P=0.0003，OR7.3，95%CI 2.2~2 4.4)。这种增加被发现是由于与HLA-DRB1*0401有关。未发现与HLADRB1*0404相关的肿瘤坏死因子微卫星等位基因。在RA组中发现3种扩展单倍型：1)HL A-DRB1*401；TNFd4；TNFa6；TNFb5；HLA-B44；HL A-CW5；HL A-A2；2)HL A-DRB1*0301；TNFd2；TNFa2；TNFb3；HL A-B8；HL A-Cw7；HL A-A1；3)TNFd5；TNFc2；TNFa2；TNFb1；HL A-B62；发现与类风湿性关节炎相关的肿瘤坏死因子微卫星似乎并不独立于第二类人类白细胞抗原相关性。
Objective. To investigate 1) tumor necrosis factor (TNF) microsatellite allele frequencies in rheumatoid arthritis (RA), and 2) associations between TNF microsatellites and RA-associated HLA specificities in order to build up extended HLA haplotypes,Methods. Eighty-five caucasoid patients with RA and 109 healthy caucasoid controls were typed for TNF microsatellites a-d using fluorescent-labeled primers and semiautomated genotyping, A further 56 RA patients who were selected for having certain HLA-DRB1 types were also typed for these TNF microsatellites, Linkage disequilibria between TNF and HLA alleles were calculated, and extended haplotypes were established.Results. The TNFa6 allele frequency was significantly increased in the RA patients compared with the controls (P = 0.0019, odds ratio [OR] 2.5, 95% confidence interval [95% CI] 1.3-4.6), an increase that was further evident in patients who were HLA-DRB1*0401 homozygous (P = 0.0003, OR 7.3, 95% CI 2.2-24.4). This increase was found to be due to association with HLA-DRB1*0401. No TNF microsatellite allele was found to be associated with HLA-DRB1*0404. Three HLA extended haplotypes were identified in the RA group: 1) HLA-DRB1*401; TNFd4; TNFa6; TNFb5; HLA-B44; HLA-Cw5; HLA-A2, 2) HLA-DRB1*0301; TNFd2; TNFa2; TNFb3; HLA-B8; HLA-Cw7; HLA-A1, and 3) TNFd5; TNFc2; TNFa2; TNFb1; HLA-B62; HLA-Cw3.Conclusion. TNF microsatellites found to be associated with RA do not appear to be independent of class II HLA associations.