Assessment of the role of EGF +61A/G and EGFR R497K polymorphism in patients with inflammatory bowel disease: A case-control study

Abstract

Aim: Epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) play an important role in the regulation of cell growth, survival, migration, apoptosis, proliferation, and differentiation. We aimed to investigate the presence of EGF (+61A/G) and EGFR R497Kpolymorphisms in patients with inflammatory bowel disease (IBD) and their associations with clinical features of the patients.

Methods: This case-control study included 91 IBD patients (45 Crohn’s disease (CD) patients and 46 ulcerative colitis (UC) patients) and 129 healthy controls (HC).  EGF and EGFR were genotyped by polymerase chain reaction and restriction fragment length polymorphism techniques to elucidate their association with clinical outcomes. The disease activity for UC and CD were assessed by Truelove-Witts index (TW) and Crohn's disease activity index (CDAI), respectively. The Montreal classification was used for disease involvement and behavior.

Results: EGFR497 AA genotype was significantly decreased in patients with UC compared with CD and HC. In addition, the patients with UC who had EGF +61 A allele had increased risk of moderate and severe disease (p=0.28; OR= 3.13; 95% CI=0.34-28.73). The patients with CD who had the EGF61 AG genotype were found to increased risk for the presence of penetrating disease (p=0.14; χ²=5.59; OR=5.00; 95% CI=1.26-19.83). EGF +61 A genotype carriers also had higher CDAI scores (p=0.19; OR=4.00; 95% CI=0.44-36.14). In addition, A+ carriers were also found to have higher requirement for anti-TNF treatment (p=0.11; OR=5.0; 95% CI=0.56-44.4).

Conclusion: In this study, EGFR 497 AA genotype was found to decrease significantly in patients with UC compared to HC and CD patients. To enlighten the mechanism, further studies with larger sample groups are needed to clarify the role of the EGF (+61A/G) and EGFR R497K genes polymorphism, and development of the etiology and pathogenesis of IBD.

Keywords

• EGF61,EGFR497,inflammatory bowel diseases,ulcerative colitis,Crohn’s disease,ulcerative colitis

İnflamatuar bağırsak hastalığında EGF +61A/G ve EGFR R497K polimorfizm rolünün değerlendirilmesi: Bir olgu-kontrol çalışması

Öz

Amaç: Epidermal büyüme faktörü (EGF) ve epidermal büyüme faktörü reseptörü (EGFR), hücre büyümesi, canlılığı, migrasyonu, apoptoz, proliferasyon ve farklılaşmasının düzenlenmesinde önemli bir rol oynamaktadır. İnflamatuar barsak hastalığı (İBH) olan hastalarda EGF (+61A/G) ve EGFR R497K polimorfizmlerinin varlığını ve hastalığın klinik özellikler ile ilişkisini araştırmayı amaçladık.

Yöntemler: Bu vaka kontrol çalışmasında 91 IBD hastası (45 Crohn hastalığı (CD) hastası ve 46 ülseratif kolit (UC) hastası) ve 129 sağlıklı kontrol (HC) vardı. EGF ve EGFR, polimeraz zincir reaksiyonu ve restriksiyon fragman uzunluğu polimorfizm teknikleri ile hastalık ve sağlıklı control grubu genotiplendirildi. Genotiplerin  hastalık ve klinik özellikleri ile ilişkileri incelendi. UC ve CD için hastalık aktivitesi sırasıyla Truelove-Witts indeksi (TW) ve Crohn hastalığı aktivite indeksi (CDAI) ile değerlendirildi. Montreal sınıflandırması hastalık tutulumu ve davranışı için kullanılmıştır.

Bulgular: Ulseratif kolit hastalarında EGFR497 AA genotipi CD ve HC'ye göre anlamlı olarak azaldığı saptanmıştır. Ek olarak, EGF +61 A alleli olan UC'li hastalarda orta ve ciddi hastalık riski artmıştır (p = 0.28; OR = 3.13; % 95 CI = 0.34-28.73). EGF +61 AG genotipine sahip olan CD'li hastalarda penetran hastalık varlığı açısından artmış risk bulundu (p = 0.14; χ2 = 5.59; OR = 5.00; % 95 CI = 1.26-19.83). EGF +61 A alleli taşıyıcılarında daha yüksek CDAI skor riski saptandı (p = 0.19; OR = 4.00; % 95 CI = 0.44-36.14). Ek olarak, CD hastalarında EGF +61 A alleli taşıyıcılarının anti-TNF tedavi gereksinimi için artmış riske sahip olduğu bulunmuştur (p = 0.11; OR = 5.0; % 95 CI = 0.56-44.4).

Sonuç: Bu çalışmada, UC'li hastalarda EGFR497 AA genotipinde HC ve CD'li hastalara kıyasla, anlamlı azalma saptandı. EGF +61A allele sahip hastalarda artmış aktivite riski saptanmıştır.  IBD'nin etiyolojisi ve patogenezinde EGF (+ 61A / G) ve EGFR R497K gen polimorfizminin rolünü açıklığa kavuşturmak için daha geniş örnek gruplarıyla daha fazla çalışmaya ihtiyaç vardır.

Anahtar Kelimeler

• EGF +61A/G,EGFR R497K,inflammatuar bağırsak hastalığı,Crohn’s hastalığı,ülseratif kolit

Kaynakça

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