Romatizmal Kalp Kapak Hastalığı Olan Türk Hastalarda IL-1Ra VNTR Gen Polimorfizminin İlişkisi Üzerine Bir Çalışma

Amaç: Romatizmal kalp kapak hastalığının (RKKH)’da dahil olduğu çeşitli otoimmün ve kronik enflamatuvar hastalıklarda, IL-1 resep-tör antagonisti (IL-1Ra) A2 allelinin uzun süreli ve şiddetli proenflamatuvar bağışıklık cevabıyla ilişkili olabileceği yönünde çalışmalar bulunmaktadır. Ancak, RKKH patogenezinde IL-1Ra varyantının ilişkisi ile ilgili çalışmalar oldukça sınırlıdır. Bu çalışmanın amacı, Türk hastalarda IL-1Ra rs2234663 değişken sayıda ardışık yineleme (VNTR) varyantları ile RKKH duyarlılığı ve/veya hastalığın şiddeti arasında bir ilişki olup olmadığını araştırmaktır.Gereç ve Yöntem: Bu vaka-kontrol çalışmasında (165 RKKH/300 kontrol) IL-1Ra VNTR için polimeraz zincir reaksiyonu (PZR) yöntemi ile genotipleme yapılmıştır. Bulgular: Hastalar ve kontroller arasında genotip ve allel frekanslarında istatistiksel olarak anlamlı fark tespit edilmiştir (p<0,001). A1 allel frekansı, RKKH hastalarında kontrol grubuyla karşılaştırıldığında, anlamlı olarak daha yüksek bulunmuştur (p=0,004; OR=3,821; %95 GA=1,459-10,005). A3 allel frekansı hasta grubunda kontrol grubuna kıyasla istatistiksel olarak anlamlı şekilde artış göstermiştir (p=0,034; OR=2,536; %95 GA=1,045-6,152). Şiddetli ve hafif kapak hasarı olan hastalar arasında genotip dağılımları istatistiksel olarak anlamlı şekilde farklı bulunmuştur (p=0,031). A2 alleli şid-detli kapak hasarı olan hastalarda hafif kapak hasarı olan hastalara göre istatistiksel olarak yüksek olarak tespit edilmiştir (p=0,003).Sonuç:IL-1Ra VNTR rs2234663 varyantlarının Türk toplumunda RKKH açısından duyarlı bireylerin tanımlanmasında kullanılabilecek uygun bir biyobelirteç olabileceği önerilmektedir.

Anahtar Kelimeler:

IL-1Ra, rs2234663, polimorfizm, romatizmal kalp kapak hastalığı, romatizmal ateş

A Study on the Relationship of IL-1Ra VNTR Gene Polymorphism in Turkish Patients with Rheumatic Heart Disease

Objective: There are studies that suggest that the IL-1 receptor antagonist (IL-1Ra) A2 allele may be associated with a long-term and severe proinflammatory immune response in various autoimmune and chronic inflammatory diseases, including rheumatic valvular heart disease (RVHD). However, studies on the relationship of the IL-1Ra variant in the pathogenesis of RVHD are very limited. The aim of this study was to investigate whether there is a relationship between IL-1Ra rs2234663 variable number tandem repeat (VNTR) variants and RVHD susceptibility and/or disease severity in Turkish patients.Material and Method: In this case-control study (165 RVHD/300 controls), we genotyped IL-1Ra VNTR using the polymerase chain reaction (PCR) method.Results: There was a statistically significant difference in genotype and allele frequencies between patients and controls (p<0.001). The A1 allele frequency was found to be significantly higher in RVHD patients compared to the control group (p=0.004; OR=3.821; 95% CI=1.459-10.005). The A3 allele showed a statistically significant increase in the patient group compared to the control group (p=0.034; OR=2.536; 95% CI=1.045-6.152). Genotype distributions were statistically significantly different between patients with severe and mild valve damage (p=0.031). The A2 allele was statis-tically higher in patients with severe valve damage compared to patients with mild valve damage (p=0.003).Conclusion:IL-1Ra VNTR can be recommended as a suitable biomarker that can be used to identify susceptible individuals in terms of RVHD susceptibility in the Turkish population.

Keywords:

IL-1Ra, rs2234663, polymorphism, rheumatic valvular heart disease, rheumatic fever,

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