The impact of smoking on clinical features of Behçet's disease patients with glutathione S-transferase polymorphisms.

OBJECTIVES: Various cancer studies have suggested that polymorphism of GSTM1 may influence the ability to detoxify chemicals in cigarette smoke. In the present study the effect of smoking on clinical features of Behçet's disease were investigated in patients having GST-M1 and/or -T1 null polymorphisms. METHODS: Ninety-seven patients meeting International Study Group Criteria for Behçet's disease (63 male, 34 female) and 172 healthy controls (94 male, 78 female) were included into the study. GST-M1 and -T1 polymorphisms were investigated using polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: Frequency of GSTM1- and/or GSTT1-null polymorphisms were comparable between the Behçet and the control groups. Smoking patients with GSTM1 null-polymorphism have decreased risk of developing papulopustuler lesions (OR=0.227 [0.063-0.818], χ2=5.463, p=0.019). Non-smoking patients with GSTM1 null-polymorphism has increased risk for having chronic arthritis (OR=5.988 [0.845-43.478]) but smoking patients with GSTM1 null-polymorphism have decreased risk (OR=0.741 [0.593-0.926]). GSTT1 null-polymorphism is associated with the presence of venous insufficiency (χ2=6.273, p=0.012, OR=2.740 [1.224-6.135]); smoking further increases the risk (χ2=7.840, OR=3.333 [1.412-7.874], p=0.005). GSTM1 null-polymorphism seemed to effect development of large vessel vasculitis (OR=1.158 [0.981-1.367], χ2=4.760, p=0.029). Male smoker Behçet patients even have more risk (OR=1.250 [0.971-1.610]). CONCLUSIONS: Several manifestations of Behçet's disease may be influenced by smoking, and this effect can be augmented in patients carrying GST gene polymorphism, which code enzymes crucial for the detoxification of chemicals.

Takayasu's arteritis in Turkey - clinical and angiographic features of 248 patients.

OBJECTIVE: Takayasu's arteritis (TA) is a chronic, inflammatory vasculitis affecting the aorta and its major branches. Although it is more prevalent in Far-East Asia, the distribution of the disease is worldwide with different vascular involvement patterns and clinical manifestations. The objective of this study was to evaluate the demographic, clinical, angiographic and prognostic features of TA patients in Turkey. METHODS: Clinical and angiographic findings of 248 TA patients (228 female, 27 male) followed at 15 Rheumatology Centers were prospectively evaluated according to a predefined protocol. RESULTS: The mean age was 40.1 years (30.2 years at the clinical onset). Clinical manifestations included constitutional symptoms in 66%, absent or diminished pulses in 88%, bruits in 77%, extremity pain in 69%, claudication in 48%, hypertension in 43% and cerebrovascular accidents (CVA) in 18% of the patients. Renal artery stenosis, aortic regurgitation and pulmonary hypertension were present in 26%, 33% and 12%, respectively. According to the new angiographic classification, type V (50.8%) and Type I (32%) were the most frequent types of involvement. Corticosteroids were the main treatment in 93% of the patients alone (9%) or in combination with immunosuppressive agents (84%). Most frequently preferred immunosuppressive agents were methotrexate (63%), azathioprine (22%) and cyclophosphamide (13%). Remission was observed at least once in 94% of the patients and sustained remission in 71% during follow-up. CONCLUSION: The demographical, clinical and angiographic findings of TA patients in our series were similar to those reported from Japan, Brazil and Colombia. Combination therapies with immunosuppressive agents were the preferred choice of treatment in Turkey.

Analysis of vascular endothelial growth factor gene 936 C/T polymorphism in patients with familial Mediterranean fever.

Vascular endothelial growth factor (VEGF) is a cytokine that promotes endothelial cell proliferation, leucocyte chemotaxis and expression of adhesion molecules and is a major mediator of vascular permeability. It has been demonstrated that VEGF directly activates neutrophils and it could promote acute recruitment of leucocytes. It is known that neutrophils are the major cell population involved in acute inflammation in familial Mediterranean fever (FMF) and the role of VEGF in these cells may be crucial. The aim of this study was to investigate whether the 936 C/T functional polymorphism of the VEGF gene is associated with susceptibility to FMF and its relationship with the main clinical features of the disease. Polymerase chain reaction-restriction fragment length polymorphism technique was used to determine 936 C/T polymorphism within the VEGF gene in 75 patients with FMF and 122 non-related healthy controls. Genotype and allele frequencies of the VEGF 936 C/T polymorphism between patients with FMF and healthy control groups were not significantly different (OR = 0.74, 95% CI = 0.40-1.37, P = 0.335 for CT genotype; OR = 1.11, 95% CI = 0.67-1.83, P = 0.700, for T allele). Although VEGF 936 TT genotype was found to be more frequent in patients with FMF than in healthy controls (6.7% vs. 1.6%, respectively), the difference was not significant (OR = 4.28, 95% CI = 0.81-22.67, P = 0.108). No associations were found between the studied polymorphism and either the clinical features such as arthritis, abdominal pain, pleuritis, myalgia, arthralgia and erysipelas-like erythema of the disease or the four common studied exon 10 mutations (M694V, M680I, V726A, M694I) of the Mediterranean fever gene. Present results suggest that VEGF gene 936 C/T polymorphism does not seem to be associated with susceptibility to FMF and its clinical manifestations.

Interleukin (IL)-12, IL-2, and IL-6 gene polymorphisms in Takayasu's arteritis from Turkey.

Takayasu's arteritis (TA) is a chronic arterial inflammation of unknown etiology involving mainly the aorta and its major branches. Genetic polymorphisms of cytokines are screened as susceptibility factors for TA in Turkey. A total of 94 patients with TA were investigated for the genetic polymorphisms of the interleukin genes IL12, IL2,and IL6 and were compared with 108 healthy control subjects using polymerase chain reaction-sequence-specific primer method. The frequencies of IL12B 1188 C allele (p = 0.03, OR = 1.7) and CC genotype (p = 0.007, OR = 3.7) were both higher in TA patients than in control subjects. TT genotype at IL2-330 (p = 0.006, OR = 2.4) and GG genotype at IL6-174 (p = 0.04, OR = 1.9) were more frequent in TA patients. Lower prevalence of GT genotype at IL2-330 (p = 0.005, OR = 0.4), CG genotype at IL6-174 (p = 0.001, OR = 0.4), and AG genotypes at IL6-598 (p = 0.01, OR = 0.4) were also detected. The polymorphism of IL-12 as well as IL-6 and IL-2 genes may contribute to susceptibility and pathogenesis of TA by altering cytokine production and inducing inflammation.