Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease

Behcet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behcet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behcet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 x 10(-8)). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production

Impaired hypothalamo-pituitary-adrenal axis in patients with ankylosing spondylitis

Background: To investigate the hypothalamic-pituitary-ad renal (HPA) axis in patients with ankylosing spondylitis (AS) and healthy controls. Methods: Forty-nine AS patients and 20 healthy controls were included. Low-dose ACTH test (LDST) was used to assess the HPA axis. Basal cortisol, stimulated peak cortisol levels, and acute-phase reactants [C-reactive protein (CIRP), erythrocyte sedimentation rate, and fibrinogen] were studied. Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index were also evaluated. Results: Patient and control groups were not different regarding age, sex, body mass index and waist circumference (WC). Basal cortisol levels did not show a significant difference between groups. However, cortisol increment after low-dose ACTH was significantly impaired in AS subjects with respect to controls (20.0 +/- 4.4 vs 24 +/- 2.2 mu g/dl, p < 0.001). Eleven AS patients had impaired cortisol peak after LDST when a cortisol cut-off is accepted as 500 nmol/l (118 mu g/dl) and none of the controls exhibited a peak cortisol responses to LDST < 500 nmol/l. Comparison of AS subjects who were receiving anti-tumor necrosis factor (TNF) (no.=23), and conventional therapy (no.=26) yielded similar basal and peak cortisol concentrations. Peak cortisol cocentrations were associated with basal cortisol, impaired cortisol response, CIRP, and fibrinogen. Impaired cortisol response (subjects with peak cortisol levels < 18 mu g/dl) was significantly correlated with basal and peak cortisol concentrations and BASDAI. Conclusion: Our results indicate an increased prevalence of subclinical glucocorticoid deficiency in AS patients. Anti-TNF treatment seems not to have effect on HPA axis. (J. Endocrinol. Invest. 33: 42-47, 2010) (c) 2010, Editrice Kurti

Determination of Bioaccumulation of Heavy Metals and Selenium in Tissues of Brown Trout Salmo trutta macrostigma Duméril 1858 from Munzur Stream Tunceli Turkey

The objective of the present work was to determine the bioaccumulation of arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), mercury (Hg), uranium (U) and selenium (Se) in gill, liver, and muscle tissues of the fresh water fish Salmo trutta macrostigma (Duméril, 1858) in Munzur Stream, Tunceli, Turkey. The highest concentrations of U (1.83 μg kg−1), Pb (119.84 μg kg−1) and Se (1.31 μg kg−1) were recorded in the gills of S. t. macrostigma. Concentrations of As (46.27 μg kg−1), Cd (109.19 μg kg−1), Hg (16.40 μg kg−1), Cu (18.19 μg kg−1) were recorded at highest levels in the liver. The results showed that there were significant differences in concentrations of As, Cd, Cu, Pb, Se, U and Hg in gill, liver and muscle tissue (p < 0.05). Heavy metals were within the edible parts of the investigated fish were in the permissible safety levels for human uses