Üveiti olan ve olmayan behçet hastalarında CPLX1 ve MEFV gen mutasyonu sıklıklarının araştırılması
Thesis Type: Expertise In Medicine
Institution Of The Thesis: Ankara University, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Turkey
Approval Date: 2013
Thesis Language: Turkish
Student: YEŞİM GEDİK OĞUZ
Supervisor: FATİME NİLÜFER YALÇINDAĞ
Open Archive Collection: AVESIS Open Access Collection
Abstract:Behçet's disease (BD) is a systemic disease which includes skin lesions, mucocutaneous, ocular, articular, vascular and central nervous system manifestations. The frequent appearance of FMF and BD within similar human populations, presence of clinically mistreated cases, emergence in the same family even in the same patient and acceptance of both diseases as auto inflammatory diseases brings to mind the possibility of common genetic background. This study aims to determine the relationship between BD and MEVF gene with the thesis of both diseases have the same genetic background, since it is already known that FMF has relation with MEVF gene. In the second part of our study, we aimed to investigate the relationship between CPLX1 gene and BD. Genome-wide association studies are made in order to determine the location of disease-associated genes from the samples of the communities where the prevalence of the disease is high. Complexin (CPLX) gene family is responsible for regulating the activity of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein which is required in vesicle fusion. Remmers and colleagues have made genome-wide association study in patients with BD and they found genetic link with the promoter region of CPLX1 genes in European patients. But this genetic association was not detected in Japanese patients. Although the mechanism is not known, exocytosis which is regulated by CPLX proteins are likely to shed light on the unknown mechanism of BD. Between November 2010 and June 2011, one hundred BD patients and 46 healthy volunteer (control group) have been studied in Ankara University Faculty of Medicine Department of Ophthalmology in accordance with the International BD Working Group criteria. The mean age was 40.7 (21-65) years in the patient group, 37.2 (21-65) years in the group of patients with ocular involvement and 44.4 (27-65) in the group of patients without ocular involvement. The mean age was 36.2 (23-62) in the control group. The evaluation of clinical findings in BD patients shows that all patients have oral aphthae, 50% have papulopustular lesions, 36% have erythema nodosum, 79% have genital ulceration, genital ulcers were more common in men (p = 0.042). 55% have arthritis, deep vein thrombosis was observed in 40 patients, 12 percent (25.5%) were female and 28 (52.8%) were male. MEFV mutations (P369S, R761H, E148Q, K695R, M694I, R202Q, F479L, A744S, M680I, M694V, V726A) were 55% in Behçet's patients and 57.4% in control group (p>0.05). The most observed mutation was R202Q (38% in patients group, 28% in control group). E148Q mutation was 16% in patients group and 10% in control group. M694V mutation was 8% in patient group. Because of R202Q mutation was observed quite often both patients and control group, we thought that it may be confounding factor and we excluded R202Q mutations from analysis. After exclusion of R202Q mutation, MEFV gene mutations were 30% in patients with BD, and 15.2% in the control group (p=0.015). E148 mutation was second frequent mutation, it was observed 14% in BD, and 10.8% in control group (p>0.05). Third frequent mutation was M694V. It was observed 8% in patients group, was not found in control group (p=0.027). F479L mutation was detected in 3% of patients group and in the was not detected in any cases of control group (p=0.035). There was no statistically significant difference between the patient and control groups in P369S, A744S, M680I, V726A mutations (p>0.05). In our study, M694I, R761H, K695 gene mutation was observed in none of the cases. MEFV gene mutations were investigated in relation with clinical findings. Deep venous thrombosis was detected 60% of patients with the M694V mutation and 22% of patients without M694V gene mutation (p=0.01). MEFV gene mutations were not associated with uveitis. In our region, the frequency of MEFV gene mutations in patients with BD, were higher than the control group. FMF and BD may have a common etiopathogenic mechanism. In particular, mutations M694V and F479L can be effective in the mechanism of the disease. DVT appears to be associated with the M694V mutation, while other mutations are not associated with clinical findings. In our study CPLX1 mutation was not detected in patient and control groups. Ivs2-5>G is a polymorphism of CPLX1 gene. This polymorphism was detected higher in ocular involvement (40.6%) and without ocular involvement (50.2%) groups than the community with minimal expected allele frequency (28%) (p G polymorphism in the control group (46.5%), were higher than expected minimal allele frequency (p G gene polymorphism in Turkish society is higher than other communities. This polymorphism was not associated with clinical symptoms. Although CPLX1 gene mutations was not detected in patients with BD, ivs2-5>G polymorphism of this gene region observed more frequent. Therefore further studies are needed to investigate the possible association between BD and CPLX1 gene region. Key Words: Behçet's Disease, Complexin 1 gene, FMF, MEFV gene, uveitis