ISSN: 2148-4902 | E-ISSN: 2536-4553
Northern Clinics of Istanbul Associations between cytokine gene polymorphisms and rheumatoid arthritis in Turkish population [North Clin Istanb]
North Clin Istanb. Ahead of Print: NCI-70845 | DOI: 10.14744/nci.2020.70845

Associations between cytokine gene polymorphisms and rheumatoid arthritis in Turkish population

Burcu Yucel1, Ceren Sümer2, ilhami Gok3, Murat Karkucak4, Emel Alemdaroglu2, Fahri Uçar5
1Istanbul Medeniyet University, Medical Faculty, Department of Medical Biology, İstanbul/Turkey
2Karadeniz Technical University, Medical Faculty, Department of Medical Biology, Trabzon/Turkey
3Kafkas University, Faculty of Engineering and Architecture, Department of Bioengineering, Kars/Turkey
4Karadeniz Technical University, Farabi Hospital, Department of Physical Medicine and Rehabilitation, Division of Rheumatology, Trabzon/Turkey
5Akdeniz University, Medical Faculty, Department of Medical Biology, Antalya/Turkey

Objective: Various cytokine polymorphisms have been associated as genetic risk factors predisposing to Rheumatoid Arthritis (RA) in different populations. To predict clinical outcome as well as response to therapy in RA, studies aimed to describe genetic markers. The aim of this study is to search for polymorphisms of 13 cytokine coding genes in Eastern Black Sea Region of Turkey.
Methods: DNAs of 49 patients and 96 healthy bone marrow and kidney donors were isolated from peripheral blood samples. Genotyping was performed using Heidelberg Cytokine Typing Tray kit. PCR products were visualized on agarose gel and results were analyzed using the interpretation scheme provided with the kit. Arlequin 3.5 software was used for the statistical analysis.
Results: No positive association was found between allele frequencies and the disease. However, a negative association was found for the IL-A -889 C allele (p=0.02, OR=0.533, Wald's 95% CI=0.318-0.893). IL-12 -1188 CC (p=0.01, OR=3.667, Wald's 95% CI=1.246-10.786), IL-4 -1098 GT (p=0.02, OR=2.405, Wald's 95% CI=1.129-5.125) genotypes were found positively associated with the RA, while IL-4 -590 CT (p=0.02, OR=0.422, Wald's 95% CI=0.201-0.886) was found negatively associated with the disease. In addition, IL-6 GG haplotype was found positively associated with the RA (p=0.02, OR=1.880, Wald's 95% CI=1.086-3.254).
Conclusion: Our findings suggest that some polymorphisms of the IL-1A, IL-2, IL-4, IL-6 and IL-12 could be responsible for the susceptibility or protective to RA in our study population. Multi-centered and large number of subjects containing studies that searching for cytokine polymorphisms will gather more information regarding to susceptibility to RA of Turkish patients.

Keywords: Rheumatoid Arthritis, Cytokine Polymorphism, PCR-SSP

Türk popülasyonunda romatoid artrit ile sitokin gen polimorfizmleri arasindaki ilişki

Burcu Yucel1, Ceren Sümer2, ilhami Gok3, Murat Karkucak4, Emel Alemdaroglu2, Fahri Uçar5
1Istanbul Medeniyet University, Medical Faculty, Department of Medical Biology, İstanbul/Turkey
2Karadeniz Technical University, Medical Faculty, Department of Medical Biology, Trabzon/Turkey
3Kafkas University, Faculty of Engineering and Architecture, Department of Bioengineering, Kars/Turkey
4Karadeniz Technical University, Farabi Hospital, Department of Physical Medicine and Rehabilitation, Division of Rheumatology, Trabzon/Turkey
5Akdeniz University, Medical Faculty, Department of Medical Biology, Antalya/Turkey

Giriş ve Amaç: Çeşitli sitokin polimorfizmleri, farklı popülasyonlarda Romatoid Artrit (RA)'ya yatkınlıkta genetik risk faktörleri olarak ilişkilendirilmiştir. RA'da tedaviye yanıtın yanı sıra klinik ilerleyişi tahmin etmek için genetik belirteçleri tanımlamayı amaçlayan çalışmalar mevcuttur. Bu çalışmanın amacı, Türkiye'nin Doğu Karadeniz Bölgesi'nde sitokin kodlayan 13farklı genin polimorfizmlerini araştırmaktır.
Yöntem ve Gereçler: 49 hasta ve 96 sağlıklı kemik iliği ve böbrek donörünün periferik kan örneklerinden DNA izolasyonu yapıldı. Genotipleme Heidelberg Cytokine Typing Tray kit kullanılarak yapıldı. PCR ürünleri agaroz jel elektroforezinde görüntülendi ve kit ile verilen yorum tablosu kullanılarak analiz edildi. İstatistik analizler için Arlequin 3.5 programı kullanıldı.
Bulgular: Allel frekansları ile hastalık arasında pozitif bir ilişki bulunamadı. IL-1A -889 C alleli hastalıkla negatif ilişkili bulundu (p=0.02, OR=0.533, Wald's 95% CI=0.318-0.893). IL-12 -1188 CC (p=0.01, OR=3.667, Wald's 95% CI=1.246-10.786), IL-4 -1098 GT (p=0.02, OR=2.405, Wald's 95% CI=1.129-5.125) genotipleri hastalıkla pozitif ilişkili bulunurken, IL-4 -590 CT (p=0.02, OR=0.422, Wald's 95% CI=0.201-0.886) genotipi hastalık ile negatif ilişkili bulundu. Ayrıca IL-6 GG haplotipi de hastalık ile pozitif ilişkili bulundu (p=0.02, OR=1.880, Wald's 95% CI=1.086-3.254).
Tartışma ve Sonuç: Sonuçlarımız IL-1A, IL-2, IL-4, IL-6 ve IL-12 genin bazı polimorfizmlerinin çalıştığımız popülasyonda RA’ya yatkınlık/ koruyuculuk ile ilişkili olabileceğini düşündürdü. Çok merkezli ve geniş hasta sayısına sahip çalışmalar ile Türk popülasyonunda RA’ya yatkınlıkta rol alan sitokin polimorfizmlerinin aydınlatılmasına katkı sağlanacaktır. (NCI-2019-0334.R1)

Anahtar Kelimeler: Romatoid Artrit, Sitokin Polimorfizmi, PCR-SSP



Corresponding Author: Burcu Yucel
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