SIRT1 Gen Polimorfizmleri ve Vitiligo Riski İlişkisi: Moleküler ve “in Siliko” Yaklaşım

Oktay Kuru, Nilgün SOLAK TEKİN, Ümmühani ÖZEL TÜRKCÜ, Sevim KARAKAŞ ÇELİK, Tuba Edgünlü
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Abstract

Aim: The aim of our study is to analyze the SIRT1 gene rs2273773, rs7895833 and rs7069102 polymorphisms and the association of SIRT1 gene and interacting genes with vitiligo disease by molecular and in silico methods. Material and Methods: The study group consisted of 78 vitiligo patients and 85 unrelated healthy controls. SIRT1 polymorphisms were determined using the Polymerase chain reaction confronting twopair primers (PCR-CTPP) method. In addition, other genes with which the SIRT1 gene interacts and gene ontology (GO) were determined using the GeneMANIA and GeneCodis 4 tools, respectively. Results: We have determined a significant difference in genotypes of rs7895833 in SIRT1 gene. Especially, the AG genotype was observed more in the group with vitiligo. It was determined that the rs7895833 G allele had a protective effect in terms of vitiligo (p=0.001). Intergene interaction analysis was also performed by in silico method, and it was shown that SIRT 1 is co-expressed with 16 genes and shares an area with only 12 genes physically interacting with 19 genes. We showed gene ontology and pathway analyzed with all relevant genes. It was determined that especially apoptosis and systemic sclerosis were associated with these genes. Conclusion: The SIRT1 rs7895833 SNP genotype and allele frequencies of vitiligo patients are significantly different from healthy controls. Our study shows that the rs7895833 polymorphism of the SIRT1 gene may be associated with vitiligo susceptibility. Considering the role of sirtuin and related genes, especially in the apoptotic pathway, its effect on vitiligo can be further investigated to elucidate the molecular aspect of the disease.
目的:通过分子和计算机方法分析SIRT1基因rs2273773、rs7895833和rs7069102的多态性,以及SIRT1基因及其相互作用基因与白癜风疾病的关系。材料与方法:研究组由78例白癜风患者和85例无关健康对照者组成。采用聚合酶链反应对抗双对引物(pcr - cttp)方法测定SIRT1多态性。此外,使用GeneMANIA和GeneCodis 4工具分别测定SIRT1基因相互作用的其他基因和基因本体(GO)。结果:我们确定了rs7895833在SIRT1基因上的基因型存在显著差异。特别是白癜风组AG基因型较多。结果表明,rs7895833 G等位基因对白癜风具有保护作用(p=0.001)。基因间互作分析结果表明,SIRT 1与16个基因共表达,仅与12个基因共享一个区域,与19个基因物理互作。我们展示了所有相关基因的基因本体和通路分析。特别是细胞凋亡和系统性硬化症与这些基因有关。结论:白癜风患者SIRT1 rs7895833 SNP基因型和等位基因频率与健康对照组存在显著差异。我们的研究表明SIRT1基因rs7895833多态性可能与白癜风易感性有关。考虑到sirtuin及其相关基因在白癜风中的作用,特别是在凋亡通路中的作用,可以进一步研究其在白癜风中的作用,以阐明该病的分子机制。
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