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

Year 2018, , 79 - 83, 20.07.2018

Resul Kahraman , Elif Sinem İplik , Turan Çalhan Abdurrahman Şahin , Bedia Çakmakoğlu

https://doi.org/10.25000/acem.416704

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

Abstract

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.

Keywords

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

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