ISSN: 1300-7777 E-ISSN: 1308-5263
The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Lymphocytic and Chronic Myelogenous Leukemia Risk in Turkish Patients [Turk J Hematol]
Turk J Hematol. 2015; 32(4): 311-316 | DOI: 10.4274/tjh.2014.0126  

The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Lymphocytic and Chronic Myelogenous Leukemia Risk in Turkish Patients

Serap Yalçın1, Pelin Mutlu2, Türker Çetin3, Meral Sarper4, Gökhan Özgür3, Ferit Avcu4
1Ahi Evran University Faculty of Engineering and Architecture, Kırşehir, Turkey
2Middle East Technical University, Central Laboratory, Department of Molecular Biology and Biotechnology, Ankara, Turkey
3Gülhane Military Medical Academy, Department of Hematology, Ankara, Turkey
4Gülhane Military Medical Academy, Cancer and Stem Cell Research Center, Ankara, Turkey

Objective: Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 superfamily and is secreted by various immune and nonimmune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between IL-18 gene polymorphisms and susceptibility to chronic lymphocytic leukemias (CLL) and chronic myelogenous leukemias (CML) in Turkish patients.
Materials and Methods: The frequencies of polymorphisms (rs61667799(G/T), rs5744227(C/G), rs5744228(A/G), and rs187238(G/C)) were studied in 20 CLL patients, 30 CML patients, and 30 healthy individuals. The genotyping was performed by polymerase chain reaction and DNA sequencing analysis.
Results: Significant associations were detected between the IL-18 rs187238(G/C) polymorphism and chronic leukemia. A higher prevalence of the C allele was found in CML cases with respect to controls. The GC heterozygous and CC homozygous genotypes were associated with risk of CML when compared with controls. However, prevalence of the C allele was not significantly high in CLL cases with respect to controls. There was only a significant difference between the homozygous CC genotype of CLL patients and the control group; thus, it can be concluded that the CC genotype may be associated with the risk of CLL. Based on our data, there were no significant associations between the IL-18 rs61667799(G/T), rs5744227(C/G), or rs5744228(A/G) polymorphisms and CLL or CML.
Conclusions: IL-18 gene promoter rs187238(G/C) polymorphism is associated with chronic leukemia in the Turkish population. However, due to the limited number of studied patients, these are preliminary results that show the association between -137G/C polymorphism and patients (CLL and CML). Further large-scale studies combined with haplotype and
expression analysis are required to validate the current findings.

Keywords: IL-18, Chronic lymphocytic leukemia, Chronic myelogenous leukemia, Single nucleotide polymorphisms


İnterlökin 18 Geninin Promotör Bölgesindeki -137G/C Polimorfizmi Türk Popülasyonunda Kronik Lenfositik ve Kronik Miyeloid Lösemi Riskini Arttırmaktadır

Serap Yalçın1, Pelin Mutlu2, Türker Çetin3, Meral Sarper4, Gökhan Özgür3, Ferit Avcu4
1Ahi Evran University Faculty of Engineering and Architecture, Kırşehir, Turkey
2Middle East Technical University, Central Laboratory, Department of Molecular Biology and Biotechnology, Ankara, Turkey
3Gülhane Military Medical Academy, Department of Hematology, Ankara, Turkey
4Gülhane Military Medical Academy, Cancer and Stem Cell Research Center, Ankara, Turkey

Amaç: İnterlökin-18 (İL-18), İL-1 süper ailesine ait bir sitokin olup, bağışıklık sistemine ait olan ve olmayan çeşitli hücrelerden salınmaktadır. Yapılan çalışmalar, İL-18’in hem anti-kanser hem de kansere öncülük eden etkilere sahip olduğunu göstermiştir. Bu çalışmanın amacı, kronik lenfositik lösemili (KLL) ve kronik miyeloid lösemili (KML) Türk hastalarda İL-18 gen polimorfizmleri ilişkisini değerlendirmektir.
Gereç ve Yöntemler: İL-18 polimorfizleri (rs61667799(G/T), rs5744227(C/G), rs5744228(A/G) ve rs187238(G/C)), 20 KLL ve 30 KML hasta ve 30 sağlıklı bireyde araştırılmıştır. Genotipleme, polimeraz zincir reaksiyonu ve DNA dizi analizi ile gerçekleştirilmiştir.
Bulgular: İL-18 geninde, rs187238(G/C) polimorfizmi ile kronik lösemi arasında anlamlı bir ilişki belirlenmiştir. KML hastalarında kontrol grubuna göre, C allelinin daha yüksek olduğu bulunmuştur. Kontroller ile karşılaştırıldığında, GC heterozigot ve CC homozigot genotipleri KML hastalarında risk oluşturmaktadır. Ancak, C alleli sıklığı kontrollere göre KLL olgularında
istatistiksel olarak anlamlı değildir. KLL hastaları ve kontrol grubunun homozigot CC genotipi arasında anlamlı farklılık vardır ve bunun sonucu olarak CC genotipi, KLL hastaları için risk taşımaktadır denilebilir. Verilerimize dayanarak, KLL ve KML hastalarında, İL-18 geninde rs61667799(G/T), rs5744227(C/G) ve rs5744228(A/G) polimorfizmleri arasında anlamlı bir ilişki yoktur.
Sonuç: İL-18 geninin promotor bölgesindeki rs187238(G/C) polimorfizmi Türk popülasyonunda kronik lösemi ile ilişkilidir. Ancak, yapılan bu çalışma, hasta sayısının sınırlı olması nedeniyle, -137G/C polimorfizmi ve hastalar (KLL ve KML) arasındaki ilişkiyi gösteren bir ön çalışma niteliğindedir. Mevcut bulguları doğrulamak için, haplotip ve gen ifade düzeyi analizleri ile birleştirilmiş daha geniş çaplı çalışmalara ihtiyaç vardır.

Anahtar Kelimeler: İL-18, Kronik lenfositik lösemi, Kronik miyeloid lösemi, Tek nükleotid polimorfizmi


Serap Yalçın, Pelin Mutlu, Türker Çetin, Meral Sarper, Gökhan Özgür, Ferit Avcu. The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Lymphocytic and Chronic Myelogenous Leukemia Risk in Turkish Patients. Turk J Hematol. 2015; 32(4): 311-316

Corresponding Author: Serap Yalçın, Türkiye


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