VİTİLİGODA İNTERLÖKİN 18 GEN POLİMORFİZMLERİNİN ANALİZİ

Öz

Amaç: Vitiligo, fonksiyonel melanositlerin kaybı ile karakterize yaygın bir pigment bozukluğudur. İmmünopatogenezi tam olarak aydınlatılamasa da cilt mikroçevresindeki inflamatuar değişikliklerin ve özellikle sitokin ekspresyonunun artmasının, melanosit disfonksiyonu ve ölümünün temel nedeni olduğu düşünülmektedir. Vitiligonun IFN-γ inhibisyonu kullanılarak tedavisi ile pozitif sonuçlar elde edilmiştir. İnterlökin 18 (IL-18), T hücrelerinde IFN-γ üretimini indükleyen ve Th1 yanıtında rolü olan önemli bir sitokindir. IL18 promotörü, çok sayıda polimorfizm içeren oldukça polimorfik bir bölgedir. Ancak bu polimorfizmlerden birçoğunun IL-18 üretimi ile ilişkili olmadığı bildirilmiştir, sadece promotördeki -137 G/C (rs187238) ve -607 C/A (rs1946518) polimorfizmlerinin promotörün aktivitesini etkilediği ve buna bağlı olarak da IL-18 üretimini etkilediği gösterilmiştir. Ayrıca bu polimorfizmlerin çeşitli otoimmün ve inflamatuar bozukluklarla ilişkili olduğu bildirilmiştir. Bildiğimiz kadarıyla, vitiligo ve IL18 gen polimorfizmleri arasındaki ilişkiyi araştıran hiçbir çalışma yoktur. Bu çalışmada, bu varyantların vitiligoya yatkınlıkla ilişkili olup olmadığının belirlenmesi için vitiligo hastalarında ve kontrol grubunda yukarıda bahsedilen rs187238 ve rs1946518 promotör polimorfizmlerinin sıklığı araştırıldı. Yöntem: Vitiligo tanılı 89 hasta ve 87 sağlıklı katılımcının, IL18 promotor polimorfizmleri PCR-RFLP yöntemi ile incelendi. Bulgular: Vitiligo hastaları, kontrol grubu ile karşılaştırıldığında IL18 rs187238 ve rs1946518 polimorfizmleri genotip ve alel frekanslarında anlamlı bir farklılık bulunamadı. IL18 rs187238'in CC genotipi frekansının, vitiligo hastalarında kontrol grubuna göre daha az olduğu görülmekle birlikte bu fark istatistiksel olarak anlamlı değildi (p=0.213). IL18 genindeki iki SNP'nin haplotip analizinde de gruplar arasında istatistiksel anlamlılığa ulaşılamadı (p=0.715). Sonuç: Sonuç olarak, elde ettiğimiz bulgular IL18 gen polimorfizmlerinin (-137 G/C (rs187238) ve -607 C/A (rs1946518)) vitiligo riski ve aktivitesi ile herhangi bir ilişkisinin olmadığını göstermektedir. Ancak, örneklem sayımızın nispeten küçük olmasından dolayı bulgularımızın ileri çalışmalarda etnik açıdan çeşitlilik içeren büyük örneklem gruplarıyla tekrarlanarak doğrulanması daha anlamlı olacaktır.

Anahtar Kelimeler

• Vitiligo
• İnterlökin 18
• Gen Polimorfizm
• rs187238
• rs1946518

ANALYSIS OF INTERLEUKIN 18 GENE POLYMORPHISMS IN VITILIGO

Öz

Objective: Vitiligo is a common pigmentary disorder caused by the destruction of functional melanocytes. Its immunopathogenesis is not completely understood, but inflammatory alterations in the skin microenvironment, and particularly increased expression of the cytokines, are thought to be essential regulators of melanocyte dysfunction and death. Treatment of vitiligo using IFN-γ inhibition has given positive responses. Interleukin-18 (IL-18) is a cytokine that plays an important role in the Th1 response, by its ability to induce IFN-γ production in T cells and natural killer cells. The IL18 promoter is highly polymorphic containing several polymorphisms which have been described in the promoter region of IL18. Most of them were not reported to be associated with IL-18 production, only the -137 G/C (rs187238) and -607 C/A (rs1946518) SNPs in the promoter affect its promoter activity and IL-18 production was demonstrated. In addition, these SNPs have been reported to be associated with several autoimmune and inflammatory disorders. To our knowledge, no study has investigated the association between vitiligo and IL18 gene polymorphisms. We investigated the frequencies of the two above-mentioned IL18 promoter alterations in vitiligo patients and control subjects to determine whether these variants might represent susceptibility factors for vitiligo. Method: IL18 promoter polymorphisms of 89 patients with vitiligo and 87 healthy participants were analyzed by PCR-RFLP method. Results: There were no significant differences in the genotype and allele frequency of IL18 rs187238, and rs1946518 SNPs when compared to vitiligo patients with healthy subjects. The frequency of the CC genotype of IL18 rs187238 tended to decrease in vitiligo patients compared to healthy subjects but was not statistically significant (p=0.213). In haplotype analysis of two SNPs in the IL18 gene also did not reach statistical significance (p=0.715). Conclusion: In conclusion, our results suggest that IL18 gene polymorphisms were not played a key role in the pathogenesis of vitiligo. In addition, because of the relatively small number of subjects, our findings are preliminary and need to be validated in further studies with larger sample sizes.

Anahtar Kelimeler

• Vitiligo
• Interleukin-18
• Gene Polymorphisms
• rs187238
• rs1946518

Kaynakça

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