Vašků Vladimír, Fiala Adam, Vašků Anna
1st Department of Dermatovenereology, St. Ann's Faculty Hospital, Faculty of Medicine, Masaryk University, 602 00 Brno, Czech Republic.
Psychiatrie Brno, Martinkova 253/7, Černá Pole, 612 00 Brno, Czech Republic.
Genes (Basel). 2025 Feb 27;16(3):288. doi: 10.3390/genes16030288.
: Several gene targets were identified for psoriasis. Some are currently being explored as potential therapeutic targets, including CCL11. Our task was to prove a possible association of single-nucleotide polymorphisms +67 G/A and -426 T/C in the eotaxin gene (CCL11, 17q 21.3) with the development and clinical aspects of psoriasis as an immune-based dermatological disease and evaluate its relationship to potential comorbidities. : In total, 460 patients with psoriasis were included in the case-control and genotype-phenotype study together with 167 control persons of similar age and sex distributions without a personal and/or family history of chronic disease of the skin. Two eotaxin gene polymorphisms were detected from isolated DNA via standard PCR, restriction analysis methods, and horizontal electrophoresis. : No significant case-control differences in the frequency of the CCL11 genotype in both polymorphisms were observed. In polymorphism +67 G/A, a significant increase in the AA genotype in patients with psoriasis guttata compared to plaque psoriasis was found ( = 0.006). A significant association of the A allele in psoriatic patients with a personal history of allergy was found ( = 0.02). The A alle was also significantly associated with a family history of psoriasis ( = 0.00008). In men, a higher risk of a delayed start of psoriasis (later than 40 years) associated with the T allele of -426 T/C polymorphism ( = 0.0007) was found. When double genotypes of both polymorphisms were evaluated, we observed significant differences in double genotype distribution between men with and without a family history of allergy (Pdg = 0.0005) and between those with and without affected siblings (Pdg = 0.03). In women with psoriasis, a higher risk of the TT genotype of -426 T/C polymorphism in patients with a personal history of diabetes ( = 0.001) as well as in patients with both a personal history of cardiovascular disease and diabetes ( = 0.00005) was proved. When double genotypes of both polymorphisms were evaluated, the significance of double genotype difference between those with and without personal history of diabetes was very high (Pdg = 0.0002). Similarly, the significance of the double genotype difference between those with and without personal history of cardiovascular diseases and diabetes was very high (Pdg = 0.000001). : CCL11 is considered one of the basic chemokines responsible for the origin and development of immune-based reactions. Based on our results, we suggest that the +67 G/A CCL11 polymorphism should be considered as a gene modulator of psoriasis in specific subgroups of patients.
已确定了几个银屑病的基因靶点。目前正在探索其中一些作为潜在治疗靶点，包括CCL11。我们的任务是证明嗜酸性粒细胞趋化因子基因（CCL11，17q21.3）中的单核苷酸多态性+67 G/A和-426 T/C与作为一种基于免疫的皮肤病的银屑病的发生和临床特征之间可能存在关联，并评估其与潜在合并症的关系。
在病例对照和基因型-表型研究中，共纳入了460例银屑病患者以及167名年龄和性别分布相似且无个人和/或家族慢性皮肤病病史的对照者。通过标准PCR、限制性分析方法和水平电泳从分离的DNA中检测到两个嗜酸性粒细胞趋化因子基因多态性。
在这两种多态性中，CCL11基因型频率在病例组和对照组之间未观察到显著差异。在多态性+67 G/A中，点滴状银屑病患者的AA基因型与斑块状银屑病相比显著增加（P = 0.006）。发现银屑病患者中具有过敏个人史的A等位基因存在显著关联（P = 0.）。A等位基因也与银屑病家族史显著相关（P = 0.00008）。在男性中，发现-426 T/C多态性的T等位基因与银屑病延迟发病（40岁以后）的风险较高相关（P = 0.0007）。当评估两种多态性的双重基因型时，我们观察到有和没有过敏家族史的男性之间双重基因型分布存在显著差异（Pdg = 0.0005），以及有和没有患病兄弟姐妹的男性之间存在显著差异（Pdg = 0.03）。在患有银屑病的女性中，证明有糖尿病个人史的患者以及有心血管疾病和糖尿病个人史的患者中-426 T/C多态性的TT基因型风险较高（P = 0.001和P = 0.00005）。当评估两种多态性的双重基因型时，有和没有糖尿病个人史的患者之间双重基因型差异的显著性非常高（Pdg = 0.0002）。同样，有和没有心血管疾病和糖尿病个人史的患者之间双重基因型差异的显著性非常高（Pdg = 0.000001）。
CCL11被认为是负责基于免疫反应的起源和发展的基本趋化因子之一。基于我们的结果，我们建议+67 G/A CCL11多态性应被视为特定患者亚组中银屑病的基因调节因子。
