Gülay GÜLBOL DURAN, İsmet Murat MELEK, Taşkın DUMAN, Ramazan GÜNEŞAÇAR

Multipl Sklerozisli Hastalarda Serum sFas, sFas Ligand Düzeyleri ile FAS ve FASLG Polimorfizmleri Arasındaki İlişkinin Araştırılması

Amaç: Multiple Sklerozis (MS) otoreaktif T lenfositlerin miyelin antijenlerine karşı gösterdiği reaksiyon sonucu ortaya çıkan otoimmün bir hastalıktır. Fas-FasL yolağı T hücre apoptozisinde önemli bir rol oynamaktadır ve otoimmun hastalıklarda Fas-FasL yolağında defektler olduğu bilinmektedir. Bu çalışmada FAS -670 A/G ve FASLG -844 T/C fonksiyonel gen polimorfizmleri ile serum sFas ve sFasL düzeylerinin MS gelişimine ve hastalığın patogenezine katkısının araştırılması amaçlanmıştır. Yöntemler: Çalışmaya 108 MS hastası ve kontrol grubu olarak da 98 sağlıklı birey dahil edilmiştir. FAS -670 A/G ve FASLG -844 T/C polimorfizmlerinin belirlenmesi için PCR-RFLP tekniği kullanılmıştır. sFas ve sFasL düzeyleri solid fazlı sandviç ELISA kiti kullanılarak ölçülmüştür. Bulgular: MS hastalarında FAS -670 AG genotipi frekansı (%55,55) sağlıklı kontrollere (%72,44) göre düşük (p=0.014), GG genotipi frekansı ise hasta grubunda (%19,44) sağlıklı kontrollere (%3,06) göre anlamlı derecede yüksek bulundu (p = 0.0001). Hasta ve kontrol grupları arasında FASLG -844 T/C polimorfizmi açısından anlamlı bir fark bulunamadı (p > 0.05). Serum sFasL düzeyleri MS grubunda, sağlıklı kontrol grubuna göre istatistiksel olarak anlamlı bir şekilde yüksek bulunmakla (p = 0.015) birlikte, sFas düzeyleri gruplar arasında benzer bulundu (p = 0.705). FAS - FASLG polimorfizmleri ile serum sFas - sFasL düzeyleri arasında anlamlı bir ilişki bulunamadı. Sonuç: Sonuçlarımız FAS -670 AG genotipinin MS riskini azaltarak (RR = 0.475, p = 0.014) koruyucu bir rol oynayabileceğini, GG genotipinin ise MS ile ilişkili güçlü bir risk faktörü (RR = 7.644, p = 0.0001) olabileceğini, serum sFasL düzeylerindeki artışın ise bu faktörün MS patogenezine katkı sunabileceğini gösterebilir.

Investigation of the Relationship Between Serum Solubl Fas (sFas), Soluble Fas Ligand (sFasL) Levels and FAS-FASLG Polymorphisms in Patients with Multiple Sclerosis

Objective: Multiple Sclerosis (MS) is an autoimmune disease caused by the reaction of autoreactive T lymphocytes to myelin antigens. Fas-FasL patway plays an important role in T cell apoptosis and It is well known that there are defects in the Fas-FasL pathway in autoimmune diseases. In this study, we aimed to investigate the effect of FAS -670 A/G and FASLG -844 T/C functional gene polymorphisms and serum sFas and sFasL levels on MS development and their contribution to the pathogenesis of the disease. Methods: 108 MS patients and 98 healthy individuals as control group were included in the study. PCR-RFLP technique was used to determine FAS -670 A/G and FASLG -844 T/C polymorphisms. Serum sFas and sFasL levels was measured using the solid phase sandwich ELISA kit. Results: FAS -670 AG genotype frequency in MS patients was lower than healthy controls (p=0.014), while GG genotype frequency was significantly higher in the patient group than healthy controls (p=0.0001). Serum sFasL levels were significantly higher in MS group compared to healthy controls (p=0.015), but sFas levels were similar between the groups (p = 0.705). There was no significant correlation between FAS - FASLG polymorphisms and sFas - sFasL levels. Conclusion: Our results suggest that FAS -670 AG genotype may play a protective role by reducing the risk (OR=0.475, p=0.014), while the GG genotype is a strong risk factor associated with MS (OR=7.644, p=0.0001), and elevated levels of serum sFasL may contribute to the pathogenesis of the disease.

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