Reich K, Westphal G, Schulz T, Müller M, Zipprich S, Fuchs T, Hallier E, Neumann C
Department of Dermatology, Georg-August-University Göttingen, Germany.
J Invest Dermatol. 1999 Aug;113(2):214-20. doi: 10.1046/j.1523-1747.1999.00654.x.
Environmental and genetic factors are thought to interact in the manifestation of psoriasis, but knowledge about the involved genes and antigens is incomplete. This study has focused on the association between psoriasis and inherited variations in xenobiotic metabolism and cytokine production as two components that may influence cutaneous immune responses to foreign substances. Polymorphisms of N-acetyltransferase 2, glutathione S-transferases T1 and M1, and promoter polymorphisms of the genes encoding for tumor necrosis factor-alpha and interleukin-10 were investigated in 151 Caucasian patients with psoriasis (100 with type I and 51 with type II psoriasis) and in 123 healthy controls. Polymorphisms were detected by polymerase chain reaction-based methods, restriction enzyme analysis, and direct sequencing. There were no significant differences in the distribution of enzyme polymorphisms or point mutations at position -1082 of the interleukin-10 promoter between the psoriasis groups and the control group. The G-->A polymorphism at position -238 of the tumor necrosis factor-alpha promoter (TNF alpha-238A allele) was more common in type I psoriasis (27%) than in the controls [9.8%; odds ratio 3.4 (95% confidence interval 1.6-7.2); p = 0.0012; pcorr = 0.018]. Surprisingly, this overrepresentation of the tumor necrosis factor alpha-238A allele was observed in male patients [4.1 (1.5-11.0); p = 0.0046; pcorr = 0.064] but not in female patients [1.8 (0.5-6.5); p = 0.5]. The G-->A polymorphism at position -308 of the tumor necrosis factor-alpha promoter was less frequent in type I psoriasis (23%) compared with controls (35.7%), although the negative association was weak [0.54 (0.3-0.97); p = 0.041; pcorr = not significant]. The distribution of the TNF alpha-238A and TNF alpha-238A alleles was similar in type II patients and controls. Our results suggest that male carriers of the G-->A polymorphism at position -238 of the tumor necrosis factor-alpha promoter are at an increased risk to develop early-onset psoriasis.
环境和遗传因素被认为在银屑病的表现中相互作用，但关于相关基因和抗原的知识并不完整。本研究聚焦于银屑病与外源性物质代谢和细胞因子产生方面的遗传变异之间的关联，这两个因素可能影响皮肤对外源性物质的免疫反应。我们对151名白种人银屑病患者（100名I型和51名II型银屑病患者）以及123名健康对照者，研究了N - 乙酰转移酶2、谷胱甘肽S - 转移酶T1和M1的多态性，以及肿瘤坏死因子 - α和白细胞介素 - 10编码基因的启动子多态性。通过基于聚合酶链反应的方法、限制性酶切分析和直接测序检测多态性。银屑病组和对照组之间，酶多态性分布或白细胞介素 - 10启动子 - 1082位的点突变无显著差异。肿瘤坏死因子 - α启动子 - 238位的G→A多态性（TNFα - 238A等位基因）在I型银屑病患者中（27%）比对照组（9.8%）更常见[优势比3.4（95%置信区间1.6 - 7.2）；p = 0.0012；校正p = 0.018]。令人惊讶的是，这种肿瘤坏死因子α - 238A等位基因的过度表达在男性患者中观察到[4.1（1.5 - 11.0）；p = 0.0046；校正p = 0.064]，而在女性患者中未观察到[1.8（0.5 - 6.5）；p = 0.5]。肿瘤坏死因子 - α启动子 - 308位的G→A多态性在I型银屑病患者中（23%）比对照组（35.7%）频率更低，尽管负相关较弱[0.54（0.3 - 0.97）；p = 0.041；校正p不显著]。II型患者和对照组中TNFα - 238A和TNFα - 238A等位基因的分布相似。我们的结果表明，肿瘤坏死因子 - α启动子 - 238位G→A多态性的男性携带者患早发性银屑病的风险增加。
