IN SİLİKO YAKLAŞIMLA SİSTEMİK LUPUS ERİTEMATOZUS’TA GENETİK VE EPİGENETİK MEKANİZMALAR: BAĞIŞIKLIK YANITI GENLERİNE ODAKLANMA

Abstract

Amaç: Sistemik lupus eritematozus (SLE), düzensiz bağışıklık tepkileri ve genetik yatkınlık ile karakterize edilen çok yönlü otoimmün bir durumdur. Bu in siliko çalışmanın amacı, SLE patogenezinde bağışıklık yanıtı genlerini incelemek ve genetik ile epigenetik düzenlemelere odaklanmaktır. Gereç ve Yöntemler: 1255 SLE hastası ve 453 kontrol grubunu içeren bu çalışma, bağışıklık yanıtı ile ilişkilendirilen genleri belirlemeyi ve hem SLE hastalarında hem de kontrol grubunda bunların ekspresyon ve DNA meti lasyon düzeylerini incelemeyi amaçlamaktadır. Çalışmada, açık erişimli bir veri tabanı olan ADEX veritabanını kullanmıştır. Bulgular: Çalışma, SLE patogenezinde on farklı şekilde ekspresyon göste ren bağışıklık yanıtı ile ilişkilendirilen genleri (FAM117B, ZNF395, PGAP3, PIK3IP1, HLA-DMB, HLA-DPA1, HLA-DRB3, HLA-DQA1, HLA-DPB1 ve CCL5) ve bunlara karşılık gelen 78 metilasyon sitesini belirlemiştir. SLE hastaların da HLA-DQA1, HLA-DMB ve CCL5’in aşırı ekspresyonu gözlenirken, diğer genlerin ekspresyonunda azalma görülmüştür. HLA-DPA1, HLA-DPB1, HLA DMB, HLA-DQA1, CCL5 ve ZNF395’in SLE’de en fazla hipermetile edilen genler olduğu bulunmuştur. HLA-DPB1, CCL5, FAM117B ve ZNF395’in CpG adalarındaki metilasyonları, bunların SLE’deki ekspresyon düzeyleri ile ilişkili bulunmuştur. Sonuç: Bu bulgular, SLE’nin genetik ve epigenetik mekanizmalarına ışık tutmakta ve bu genlerin bağışıklık düzensizliği ve hastalık ilerlemesi üze rindeki önemini vurgulamaktadır. Bu genlerin fonksiyonel önemine ilişkin daha fazla araştırma, SLE patogenezine ve potansiyel terapötik hedeflere yönelik değerli bilgiler sağlayabilir.

Keywords

• Sistemik lupus eritematozus
• İmmün yanıtla ilişkili genler
• HLA-DPB1
• Epigenetik düzenleme
• FAM117B
• ZNF395

IN SILICO APPROACH TO GENETICS AND EPIGENETIC MECHANISMS IN SYSTEMIC LUPUS ERYTHEMATOSUS: FOCUS ON IMMUNE RESPONSE GENES

Abstract

Objective: Systemic lupus erythematosus (SLE) is a multifaceted autoim mune condition characterised by irregular immune reactions and genetic susceptibility. The aim of this in silico study was to investigate immune response genes during SLE pathogenesis, focusing on genetic and epige netic regulation. Materials and Methods: This study involving 1255 patients with SLE and 453 control subjects aimed to identify genes associated with the immune response and examine their expression and DNA methylation levels in both patients with SLE and controls. The study design utilized the ADEX open-access database. Results: The study identified 10 differentially expressed immune respon se-related genes (FAM117B, ZNF395, PGAP3, PIK3IP1, HLA-DMB, HLA DPA1, HLA-DRB3, HLA-DQA1, HLA-DPB1, and CCL5) in SLE pathogenesis, with 78 corresponding methylation sites. Upregulation of HLA-DQA1, HLA-DMB, and CCL5 was observed in patients with SLE, whereas the rema ining genes exhibited decreased expression. HLA-DPA1, HLA-DPB1, HLA DMB, HLA-DQA1, CCL5, and ZNF395 were found to be the most hyper methylated genes in SLE. Methylation of the CpG islands of HLA-DPB1, CCL5, FAM117B, and ZNF395 is correlated with their expression levels in SLE. Conclusion: Our findings shed light on the genetic and epigenetic mecha nisms underlying SLE and underscore the importance of these genes in immune dysregulation and disease progression. Further research on the functional significance of these genes could provide valuable insights into the pathogenesis of SLE and potential therapeutic targets.

Keywords

• Systemic lupus erythematosus
• Immune response-related genes
• HLA-DPB1
• epigenetic regulation
• FAM117B
• ZNF395

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