Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study.

OBJECTIVE: Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. METHODS: Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. RESULTS: We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10(-8)), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10(-8)). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 10(-5)) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. CONCLUSION: Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Demographic and clinical features of gout patients in Turkey: a multicenter study.

Gout results from multifactor interactions between gender, age, genetic and environmental factors. Environmental factors underlying gout and precipitating factors triggering acute attacks might vary in different populations with different lifestyles. In this study, we aimed to collect data regarding the demographic and clinical features, comorbid factors, and precipitating factors associated with the initiation of acute attacks in gout patients in Turkey. A total of 312 patients were included in this study (mean age, 58.8 ± 13.8 years; female/male ratio, 55/257). The demographic features, alcohol intake, clinical and laboratory features, and comorbid conditions including obesity, diabetes mellitus, hyperlipidemia, hypertension, and coronary heart disease were noted in a standard questionnaire. Precipitating factors initiating acute attacks (if any) were also noted. The patients were divided into 4 groups according to the region of location as central Anatolian region, southeast Anatolian region, Aegean region, and Trakya region. Our results were compared according to the gender and the location of the patients. The mean age at the start of the symptoms was 10 years higher in women (60.4 ± 14.8 and 50.6 ± 13.5 years in women and men, respectively, p < 0.001).Obesity was present in 40.1 %, diabetes mellitus in 17.9 %, hyperlipidemia in 30.1 %, hypertension in 53.5 %, coronary artery disease in 17 %, and nephrolithiasis in 21.8 % of patients. Precipitating factors triggering gout flares were as follows: diet (high consumption of meat or fish) in 46.5 %, alcohol consumption in 15.7 %, diuretics in 8.3 %, diet or diuretics in 5.1 %, diet or alcohol in 4.5 %, diet or alcohol or diuretics in 1.6 %, others in 4.2 %, and none in 14.1 %. The presence of diabetes and diuretic use was more common among women. Use of diuretics is a more common trigger for gout flares among women. On the other hand, various comorbid conditions, such as obesity and hypertension, and triggers for gout flares may differ between patients living in different geographic regions. In summary, we reported the first data regarding clinical and demographic characteristics of gout in Turkey. The majority of our patients could describe at least one "trigger" that initiated gout flare. Both comorbid conditions and triggers of attack might differ between men and women, and in different geographic areas. Better knowledge of the modifiable risk factors can be useful for the management strategy to optimize long-term patient outcomes in local clinics.

Asymmetric dimethylarginine and nitric oxide levels as signs of endothelial dysfunction in Behcet's disease.

Behcet's disease (BD) has been known for many years, yet the etiology of the systemic vasculitis remains unknown. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase. ADMA is involved in endothelial dysfunction in various vascular diseases and its level in BD is unclear. This study was performed to evaluate the relationship between ADMA and NO levels in plasma of patients with BD. There were 3 groups of 30 subjects: (a) controls, (b) BD patients with mucocutaneous involvement, and (c) BD patients with vascular involvement. Plasma NO levels were assayed by spectrophotometry and plasma ADMA levels were assayed by an ELISA test. Plasma ADMA levels were higher in both groups of BD patients than in the controls; the ADMA levels were higher in the BD patients with vascular involvement than in the mucocutaneous group. Plasma NO levels were lower in both groups of BD patients than in controls; plasma NO levels were lower in the BD patients with vascular involvement than in mucocutaneous group. In the combined groups of 60 BD patients, there was significant inverse correlation between the plasma concentrations of ADMA and NO (r = -0.570, p <0.001). Plasma lipid profiles did not differ significantly between the BD patients and the controls. These results are evidence for increased plasma ADMA levels and decreased plasma NO levels as risk factors for cardiovascular events in BD patients. Inhibition of NO synthesis by ADMA may contribute to vascular involvement in BD.

Evaluation of joints using Tc 99m-MDP bone scintigraphy in patients with familial Mediterranean fever: should bone scans be used for diagnosis and follow-up?

Familial Mediterranean fever (FMF) is an autosomal recessively-inherited disorder typically manifested by recurrent attacks of fever and polyserositis. The articular disease occurs in 50-70% of patients. Bone scintigraphy is more sensitive in the diagnosis of arthritis than clinical examination or conventional radiological imaging, allowing earlier diagnosis through the visualization of disease in multiple sites. To assess joint involvements in FMF patients with or without joint symptoms, bone scintigraphy was performed in 36 patients with FMF and in 25 controls. There was arthritis in 72% of patients. Of these, 65% knee, 42% ankle, 50% sacroiliac, 8% elbow, 8% wrist, 4% sternoclavicular and 4% hip involvements were found. The sacroiliac joints with sacroiliac index higher than 1.34 were diagnosed as sacroiliitis, which was higher than 2 SD of normal. FMF is frequently associated with joint disease such as knee and ankle arthritis and sacroiliitis. This high incidence of sacroiliitis in our study has not been previously reported. This difference could be explained by the different methodology used for the screening of the joints. Thus, we recommend that bone scintigraphy can be used in patients with FMF to determine the presence of arthritis, especially in sacroiliac joints, even asymptomatic.

Assessment of aortic stiffness and ventricular diastolic functions in patients with Behçet's disease.

BACKGROUND: Behçet's disease is a systemic vasculitis in which studies have given conflicting results about ventricular diastolic functions. However, tissue Doppler echocardiography has never been used in any of these studies. Aortic stiffness, a cardiovascular risk factor, may also precede ventricular dysfunction. OBJECTIVES: The aim of this study was to assess aortic stiffness and biventricular diastolic functions in patients with Behçet's disease. METHODS: A total of 26 patients with Behçet's disease (mean age; 33+/-10 years) and 20 age- and sex-matched controls (mean age; 33+/-7 years) were included. Aortic stiffness was evaluated by aortic strain and distensibility. Ventricular diastolic functions were evaluated with both conventional and tissue Doppler echocardiography. Mitral E and A wave, E/A ratio of E wave, deceleration time, and isovolumic relaxation time were calculated. RESULTS: There was no significant difference in diastolic Doppler parameters between patients and controls. Similarly, there was no significant difference in mitral annular E and A velocities between these two groups. Aortic strain in patients with Behçet's disease was found to be significantly less than in the controls (8.3+/-4.9% and 15.7+/-2.7% respectively, p<0.001). Aortic distensibility was also significantly low in patients with Behçet's disease when compared to controls (0.45+/-0.28 and 0.78+/-0.13 respectively, p<0.001). Beta index values were significantly high in Behçet's patients (7.23+/-5.93 and 2.69+/-0.55 respectively, p<0.001). CONCLUSION: No significant diastolic dysfunction was found in left and right ventricles in patients with Behçet's disease by using both conventional and tissue Doppler echocardiography. However, an increase in aortic stiffness was found, suggesting an inflammatory involvement of proximal aorta.

Platelet-activating factor and P-selectin activities in thrombotic and nonthrombotic Behçet's patients.

OBJECTIVE: The aim of this study was to compare plasma Platelet-activating factor (PAF) and P-selectin (CD62P) activities in Behçet's disease patients with and without thrombosis. METHODS: In this cross-sectional and descriptive study, 30 consecutive Behçet's patients were included, 15 of them with venous thrombosis. All patients were also divided into two subgroups according to the presence or absence of clinical activity. Plasma PAF levels, basal and Ca++ ionophore (A23187)-induced leukocyte (cellular) PAF activities, and platelet-rich plasma DeltaCD62P activity (the mean fluorescent density difference between CD62P phycoerythrin-positive and -negative stains) were evaluated. RESULTS: In the thrombotic group, plasma PAF (P=0.001), basal leukocyte PAF (P=0.017), induced leukocyte PAF (P=0.024), and DeltaCD62P (P=0.023) levels were significantly higher than in the nonthrombotic group. In the whole group of Behçet's patients, there was a positive correlation between plasma PAF and DeltaCD62P levels (r=0.533, P=0.002). When we compared clinically active and inactive patients with respect to the above parameters, there was no significant difference, irrespective of thrombosis. Plasma PAF (P=0.001), basal leukocyte PAF (P=0.004), and DeltaCD62P (P=0.038) levels were significantly higher in the presence of both clinical activity and thrombosis than of clinical activity alone. CONCLUSION: Platelet-activating factor and CD62P may contribute to endothelial injury and thrombosis development in Behçet's disease. These two parameters seem related to the presence of thrombosis rather than clinical activity.

Paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome): a report of two cases and review of the literature.

We report two cases of paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE) associated with prostatic adenocarcinoma. One of the patients was positive for Helicobacter pylori and the other had secondary bone metastases. In the latter, the clinical picture of RS3PE developed after surgical intervention for the primary lesion. On physical examination, while the hands and feet were swollen in the first patient, pitting edema was present only at the feet of the other. All joints of the affected hands and feet were painful. Serological tests including rheumatoid factor, antinuclear antibody, and human leukocyte antigen B27 were all negative. Response to low-dose corticosteroid treatment was delayed in the first patient, but the symptoms were relieved better in the second one.

Autoimmune thyroid diseases in patients with chronic fasciolosis.

BACKGROUND: The prevalence of autoimmune thyroid diseases and autoantibodies in patients with chronic fasciolosis (CF) was investigated. METHODS: Thyroid function of 32 patients with CF and 72 patients without fasciolosis infection was evaluated biochemically. Thyroid hormones, antithyroglobulin antibodies (TgAb) and antithyroid peroxidase antibodies (TPOAb) were measured. RESULTS: In patients with CF, the prevalences of autoantibodies against thyroid peroxidase and thyroglobulin were 21.9% (7/32) and 15.6% (5/32) respectively. However, thyroid function disorder was identified in only 3 (9.4%) cases. In the control group, TPOAb and TgAb were determined in 2 (2.7%) cases, but no one had thyroid function disorder. The prevalences of thyroid autoantibodies (chi 2: 7.948, p < 0.01) and autoimmune thyroid diseases (chi 2: 4.007, p < 0.05) were significantly higher in the CF group. CONCLUSIONS: The high prevalence of TPOAb and TgAb in CF suggests that patients with CF should be evaluated for autoimmune thyroid disorders at the time of diagnosis and during the follow-up period.