A TNF-alpha promoter polymorphism is associated with juvenile onset psoriasis and psoriatic arthritis
A TNF-alpha promoter polymorphism is associated with juvenile onset psoriasis and psoriatic arthritis
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DOI：
10.1111/1523-1747.ep12337469
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发表时间：
1997-10-01
影响因子：
6.5
通讯作者：
MarkerHermann, E
中科院分区：
文献类型：
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作者：
Hohler, T;Kruger, A;MarkerHermann, E
肿瘤坏死因子-α被认为是银屑病发病机制中的重要介质之一。据报道，青少年型银屑病与主要组织相容性复合体编码的HLA-Cw 6抗原有很强的相关性，但尚不清楚Cw 6本身或密切相关的基因是否参与发病。本研究的重点是主要组织相容性复合体编码的肿瘤坏死因子-α基因启动子多态性与银屑病和银屑病关节炎的关联。通过序列特异性寡核苷酸杂交和直接测序，在高加索青少年银屑病和银屑病关节炎患者以及健康对照中寻找肿瘤坏死因子-α启动子多态性。60例患者中有23例存在肿瘤坏死因子-α启动子-238位点突变（38%; P < 0.0001; P（corr）< 0.008），62例患者中有20例（32%; p < 0.0003; p（corr）< 0.03），相比之下，99名白人对照中有7名（7%）。银屑病组中该突变的纯合子显著增加，另一个位于-308位的突变在患者和对照组中的比例相似。我们的研究显示肿瘤坏死因子-α启动子-238位点多态性与银屑病和银屑病关节炎密切相关。我们的研究结果表明，这种启动子多态性本身或与肿瘤坏死因子α连锁不平衡的基因易患银屑病。
Tumor necrosis factor-alpha is considered to be one of the important mediators in the pathogenesis of psoriasis. A strong association of juvenile onset psoriasis with the major histocompatibility complex encoded HLA-Cw6 antigen has been reported but it is unclear whether Cw6 itself or a closely linked gene is involved in the pathogenesis. This study has focused on the association of promoter polymorphisms of the major histocompatibility complex encoded tumor necrosis factor-alpha gene with psoriasis and psoriatic arthritis. Tumor necrosis factor-alpha promoter polymorphisms were sought by sequence-specific oligonucleotide hybridization and by direct sequencing in Caucasian patients with juvenile onset psoriasis and with psoriatic arthritis and in healthy controls. A mutation at position -238 of the tumor necrosis factor-alpha promoter was present in 23 of 60 patients (38%; p < 0.0001; p(corr) < 0.008) with juvenile onset psoriasis and in 20 of 62 patients (32%; p < 0.0003; p(corr) < 0.03) with psoriatic arthritis, compared with seven of 99 (7%) Caucasian controls. There was a marked increase of homozygotes for this mutation in the psoriasis group, Another mutation at position -308 was found in similar proportions of patients and controls. Our study shows a strong association of the tumor necrosis factor-alpha promoter polymorphism at position -238 with psoriasis and psoriatic arthritis. Our findings suggest that this promoter polymorphism itself or a gene in linkage disequilibrium with tumor necrosis factor-alpha predispose to the development of psoriasis.