Mahmut Huntürk ATİLLA, SİBEL ÖZDAŞ, Sibel BAŞTİMUR, Talih ÖZDAŞ, Sami Engin MUZ, Isilay OZ, İpek Canatar İpek CANATAR

Nazal polipozis’e eşlik eden IL5 (-746), IL6 (-174) ve IL18 (-607) gen polimorfizimleri

GİRİŞ ve AMAÇ: Nazal polipozis (NP), nazal mukozanın en sık karşılaşılan patolojik değişikliği olup, mukozal inflamasyon ile karakterize iyi huylu kronik bir hastalığıdır. Bu çalışmada, NP hastalarında yaygın olarak gözlenen İnterlökin (IL)5, IL6 ve IL18 gen promotor bölgesinde yer alan sırasıyla -746 C/T, -174 G/C ve -607 C/A tek nükleotidlik polimorfizmleri (SNPs) ile NP arasındaki ilişkiyi araştırmaktır. YÖNTEM ve GEREÇLER: Çalışmaya 87 NP’li hasta ve 76 kontrol olmak üzere 163 hasta dahil edilerek, polimorfizmler Snap-Shot ile genotiplendirildi. SNP'lerin bağlantı dengesizliğini değerlendirmek, allel, genotip ve haplotip frekanslarının analizi için bir lojistik regresyon modeli olan SNPStats kullanıldı. MDR ile polimorfizmlerin birbiriyle ve klinik değişkenlerle arasındaki etkileşimler değerlendirildi. BULGULAR: Çalışmamızda, IL5 ve IL18 SNP’lerinin varlığı, majör allellerinin ve CC genotiplerinin frekansı NP'de yüksekti (sırasıyla, P< 0.001ve P< 0.001; P< 0.001 ve P< 0.001; P= 0.023 ve P= 0.006). Ayrıca IL18 SNP, aspirin intoleransı ve astımatik NP’lilerde daha sık gözlendi (P= 0.013 ve P= 0.045). Bununla birlikte IL5-IL6-IL18 CGC haplotipinin frekansı NP’li hasta grubunda yüksekti (P< 0.0001). MDR analizi ile tespit edilen en iyi tek-lokus modeline göre IL18 CC genotipinin, iki-lokus modeline göre IL5_IL18’in majör allelli içeren diplotiplerinin artmış-NP riski ile ilişkili olduğu bulundu (P= 0.006, P< 0.0001). IL5 genotiplerinin ve IL5_IL6 diplotiplerininin NP'de risk paterni IL18’ün genotipine bağlı olduğu gözlendi (P< 0.0001). Ayrıca NP-pozitif aile öyküsüne sahip bireylerin 16-kat artmış NP riski taşıdığı gözlenmiştir (P= 0.0004). TARTIŞMA ve SONUÇ: Sonuç olarak, çalışmamız IL5 (-746) ve IL18 (-607) polimorfizmlerinin nazal polipozis için predispozan faktörler olduğunu göstermiştir. Nazal polipoziste IL5 (-746) ve IL18 (-607) SNP’lerinin gen aktivitesi üzerindeki sonuçlarını araştıran ileri fonksiyonel çalışmalara ihtiyaç vardır.

Association of the IL5 (-746), IL6 (-174) and IL18 (-607) gene polymorphisms in nasal polyposis

INTRODUCTION: Nasal polyposis (NP) is a benign chronic disease characterised by mucosal inflammation. In this study, to investigate the relationship between -746 C/T, -174 G/C and -607 C/A single nucleotide polymorphisms (SNPs) which are Interleukin (IL) 5, IL6 and IL18 gene promoter and NP METHODS: A total 163 patients of 87 with NP and 76 controls were included in the study, and genotyped with Snap-Shot. SNPStats, a logistic regression model, MDR. RESULTS: In our study, the presence of IL5 and IL18SNPs, the frequency of major alleles CC genotypes were significantly higher in the patient group (respectively P< 0.001ve P< 0.001; P< 0.001 ve P< 0.001; P= 0.023 ve P= 0.006). In addition, IL18SNP was observed more frequently in patients with NP with aspirin intolerance and asthma (P= 0.013, P= 0.045). However, the frequency of IL5-IL6-IL18 CGC haplotype was high in the patient group with NP (P< 0.0001). According to the best single-locus model detected by MDR analysis, IL18 CC genotype was found to be associated with increased-NP risk of IL-5_IL18 containing major alleles according to the two-locus model (P= 0.006, P< 0.0001). IL5 genotypes and IL5_IL6 diplotypes were observed to be linked to the genotype of IL18, risk pattern in NP (P< 0.0001). It was also observed that individuals with NP-positive family history had a 16-fold increased risk of NP (P= 0.0004). However, a synergistic interaction was observed between IL18 genotypes and the clinical variable aspirin intolerance (P< 0.0001). DISCUSSION AND CONCLUSION: The polymorphisms IL5 (-746) and IL18 (-607) may be predisposing factors for nasal polyposis.

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