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非节段性白癜风的昼夜节律钟基因表达和多态性。

Circadian clock gene expression and polymorphism in non-segmental vitiligo.

机构信息

Andrology and S.T.Ds, Faculty of Medicine, Menoufia University, Shebin AlKom, Egypt.

Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University, Shebin AlKom, Egypt.

出版信息

Mol Biol Rep. 2024 Jan 18;51(1):142. doi: 10.1007/s11033-023-09109-6.

Abstract

BACKGROUND

Vitiligo is an acquired and progressive mucocutaneous disease with the damage of functioning epidermal melanocytes. Metabolic syndrome is associated with inflammatory skin diseases incorporating vitiligo. The circadian dysfunction triggers the pathogenesis of metabolic diseases, so our study aimed to determine the relationship between aryl hydrocarbon receptor nuclear translocator-like gene, a ligand-activated transcription factor and sensor of environmental chemicals, expression and polymorphism with non-segmental vitiligo, as well as its effect on lipid profile.

METHODS

This case-control study was handled on 50 non-segmental vitiligo patients (generalized (12) and localized type (focal; 24 and acrofacial; 14)) and 50 matched controls. Each subject was proposed for full history taking, clinical examinations, serum lipid profile, and measurement of BMAL1 gene expression in the blood, and BMAL1 rs2279287 polymorphism of DNA extract from whole blood by real time-PCR.

RESULTS

We identified that total cholesterol, triglyceride, and low-density lipoprotein were significantly higher, but high-density lipoprotein was significantly lower in non-segmental vitiligo patients than in the control group. A significant increase in circadian gene expression in non-segmental vitiligo patients was observed, with more detection of the BMAL1 T/C genotype (92%) than the T/T genotype. There was a significant positive relationship between the level of the circadian gene and the vitiligo patient's age, age of onset, and VIDA Score. The level of the circadian gene at Cutoff  ≥ 1.16 can predict the prognosis of vitiligo with a sensitivity of 78%, specificity of 84%, and accuracy of 81%.

CONCLUSION

The circadian gene has an active role in the progress of non-segmental vitiligo and targeting this gene could have a significant impact on its management.

摘要

背景

白癜风是一种获得性、进行性的黏膜皮肤疾病,其功能表皮黑素细胞受损。代谢综合征与包括白癜风在内的炎症性皮肤病有关。昼夜节律功能障碍引发代谢性疾病的发病机制,因此我们的研究旨在确定芳香烃受体核转位蛋白样基因(一种配体激活的转录因子和环境化学物质的传感器)的表达和多态性与非节段性白癜风的关系,以及其对血脂谱的影响。

方法

本病例对照研究纳入了 50 例非节段性白癜风患者(全身性[12 例]和局限性类型[局限性[24 例]和肢端型[14 例])和 50 例匹配对照。对每位受试者进行详细病史采集、临床检查、血清血脂谱检测,并采用实时 PCR 检测血中 BMAL1 基因表达和全血 DNA 提取的 BMAL1 rs2279287 多态性。

结果

我们发现非节段性白癜风患者的总胆固醇、甘油三酯和低密度脂蛋白显著升高,而高密度脂蛋白显著降低。非节段性白癜风患者昼夜节律基因表达显著增加,检测到 BMAL1 T/C 基因型(92%)多于 T/T 基因型。昼夜节律基因水平与白癜风患者的年龄、发病年龄和 VIDA 评分呈显著正相关。昼夜节律基因水平 Cutoff≥1.16 可预测白癜风的预后,其灵敏度为 78%,特异性为 84%,准确性为 81%。

结论

昼夜节律基因在非节段性白癜风的进展中具有活跃作用,针对该基因可能对其治疗有重大影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aacb/10796645/00583dd657b4/11033_2023_9109_Fig1_HTML.jpg

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