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波兰北部人群中肿瘤坏死因子-α基因启动子区域多态性与早发性寻常型银屑病的关联

Associations of promoter region polymorphisms in the tumour necrosis factor-alpha gene and early-onset psoriasis vulgaris in a northern Polish population.

作者信息

Nedoszytko B, Szczerkowska-Dobosz A, Zabłotna M, Gleń J, Rebała K, Roszkiewicz J

机构信息

Department of Dermatology, Venereology and Allergology, Medical Uniersity of Gdansk, Gdansk, Poland.

出版信息

Br J Dermatol. 2007 Jul;157(1):165-7. doi: 10.1111/j.1365-2133.2007.07993.x. Epub 2007 Jun 6.

Abstract

BACKGROUND

Tumour necrosis factor (TNF)-alpha is considered to be an important mediator in the pathogenesis of psoriasis. Increased levels and activity of this cytokine have been observed in blood and skin of patients with psoriasis. As certain allelic variants of the TNF-alpha gene are associated with increased or decreased production of TNF-alpha, the disturbed cytokine balance may be under genetic control.

OBJECTIVES

To investigate the potential association of TNF-alpha promoter alleles within subtypes of psoriasis compared with healthy controls in a northern Polish population.

METHODS

We analysed 166 patients with psoriasis vulgaris (134 with type I and 32 with type II) and 65 healthy controls. The polymorphisms -238G/A and -308G/A in the promoter region of the TNF-alpha gene were typed using the amplification refractory mutation system-polymerase chain reaction method.

RESULTS

We found that the TNF-alpha-308A allele frequency was significantly decreased among patients with early-onset psoriasis in comparison with control subjects (7.5% vs. 15.4%, P = 0.022), whereas in the same patients the frequency of the TNF-alpha-238A allele was significantly increased as compared with the controls (16.8% vs. 3.1%, P = 0.000017, odds ratio 8.79, 95% confidence interval 2.606-29.678). Patients with early-onset psoriasis with -238 genotype GA or AA were found more often among those with age at onset < 25 years in comparison with those with genotype GG (31.7% vs. 9.1%, P = 0.0312). We also found that the mean +/- SD age at onset among -238A carriers was significantly lower in comparison with that associated with the -238GG genotype (13.5 +/- 7.4 vs. 19.2 +/- 9.9 years, P = 0.0132).

CONCLUSIONS

Our study confirming the association between -238 G/A TNF-alpha promoter polymorphism and early-onset psoriasis vulgaris in the northern Polish population suggests that the -238A variant may contribute not only to a predisposition to psoriasis vulgaris but also to the disease phenotype.

摘要

背景

肿瘤坏死因子(TNF)-α被认为是银屑病发病机制中的一种重要介质。在银屑病患者的血液和皮肤中已观察到这种细胞因子水平和活性的升高。由于TNF-α基因的某些等位基因变体与TNF-α产生的增加或减少相关,细胞因子平衡紊乱可能受基因控制。

目的

在波兰北部人群中,研究银屑病各亚型中TNF-α启动子等位基因与健康对照之间的潜在关联。

方法

我们分析了166例寻常型银屑病患者(134例I型和32例II型)和65例健康对照。采用扩增阻滞突变系统-聚合酶链反应方法对TNF-α基因启动子区域的-238G/A和-308G/A多态性进行分型。

结果

我们发现,早发型银屑病患者中TNF-α -308A等位基因频率与对照相比显著降低(7.5%对15.4%,P = 0.022),而在同一患者中,TNF-α -238A等位基因频率与对照相比显著升高(16.8%对3.1%,P = 0.000017,优势比8.79,95%置信区间2.606 - 29.678)。与基因型GG的患者相比,早发型银屑病且-238基因型为GA或AA的患者在发病年龄<25岁的人群中更常见(31.7%对9.1%,P = 0.0312)。我们还发现,-238A携带者的平均发病年龄±标准差与-238GG基因型相关的平均发病年龄相比显著更低(13.5±7.4对19.2±9.9岁,P = 0.0132)。

结论

我们的研究证实了波兰北部人群中-238 G/A TNF-α启动子多态性与早发型寻常型银屑病之间的关联,表明-238A变体不仅可能导致寻常型银屑病的易感性,还可能影响疾病表型。

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