Cytochrome P450 polymorphisms in patients with Behcet's disease.

OBJECTIVES: Although the etiopathogenesis of Behcet's disease (BD) remains unknown, increased neutrophil functions such as chemotaxis, phagocytosis and excessive production of reactive oxygen species, including superoxide anion, may be responsible for the oxidative tissue damage observed in BD. Cytochrome P-450 are a multigene family of enzymes involved in the detoxification and occasional activation of a wide variety of chemicals. Our aim was to investigate CYP2C9 and CYP2C19 polymorphisms in patients with BD. METHODS: Sixty-two subjects with BD and 107 healthy control subjects were enrolled in the study. Polymorphisms of CYP2C9 and CYP2C19 were performed by real-time PCR with a LightCycler instrument. We researched associations between CYP polymorphisms and BD. RESULTS: The frequencies of wild-type and heterozygous CYP2C19*2 genotypes were 66.1% and 33.9% in the patients and 83.2% and 16.8% in the controls, respectively. There was a 2.53-fold increased risk of Behcet's disease in individuals with the CYP2C19*2 heterozygous genotype (OR = 2.53; 95% CI, 1.22-5.25) when compared with the control group. But the CYP2C9*2, CYP2C9*3 and CYP2C19*3 gene polymorphisms were not related to an increased risk of developing BD. CONCLUSIONS: We observed that patients with BD presented with a higher prevalence of the heterozygous CYP2C19*2 genotype. Hereditary deficiencies of this enzyme activity may lead to an imbalance between pro- and antioxidant systems, resulting in the formation of excessive reactive oxygen species.

GSTM1 and GSTT1 null genotypes as possible heritable factors of rosacea.

PURPOSE: Rosacea might be related to an increased activity of reactive oxygen species (ROS) and deficient function of the antioxidant system. Glutathione S-transferases (GSTs) play a primer role in cellular defense against electrophilic chemical species and radical oxygen species. We hypothesized that increased ROS activity or decreased antioxidant potential, possibly induced by GST gene polymorphism, might have a pathogenic role in rosacea. METHODS: The study group consisted of 45 patients with rosacea and 100 control subjects. DNA samples were isolated from blood samples using high pure polymerase chain reaction (PCR) Template preparation Kit. The GSTM1, GSTT1, and P1 polymorphisms were detected using a real-time PCR and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of rosacea were examined using logistic regression analyses to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: GSTM1 and GSTT1 null genotypes were found to be statistically different from control (P=0.005, P=0.009, respectively), and associated with an increased risk of rosacea (OR [95% CI]: 2.84 [1.37-5.89]; OR [95% CI]: 2.68 [1.27-5.67], respectively). There was a statistically significant relationship between both null combination of the GSTM1 and GSTT1 genotype polymorphisms and rosacea (P=0.003, OR [95% CI]: 4.18 [1.57-11.13]). There were no statistically significant differences between patient and control groups for the GSTP1 Ile/Ile, Ile/Val, and Val/Val genotypes (P>0.05). CONCLUSION: We demonstrated a significant association between the GSTT1 and/or GSTM1 null genotypes and rosacea. However, the potential role of GSTs as markers of susceptibility to rosacea needs further studies in larger patient groups.

A high prevalence of parvovirus B19 DNA in patients with psoriasis.

Psoriasis is a common inflammatory skin disease. Infectious models are considered to be of pathophysiological importance in psoriasis. The immunological profile of stable psoriasis plaques suggests that viral antigens may be important. Human parvovirus B19 (PVB19) is a single-stranded DNA virus that causes various clinical symptoms. Several case reports have suggested associations between PVB19 infection and various chronic autoimmune and dermatologic diseases. There has so far been no information regarding the role of PVB19 in psoriasis, except psoriatic arthritis. In this report, to investigate the role of PVB19 in psoriasis, we analyzed PVB19 DNA of peripheral blood from psoriatic patients (n = 47) in comparison with blood donors (n = 20). We also determined the presence of anti-PVB19 IgG and IgM antibodies by using enzyme-linked immunosorbent assay (ELISA). We found that the presence of PVB19 DNA in patients with psoriasis (38%) was significantly higher than in controls (0%, P < 0.01). Anti-PVB19 IgG antibodies were detected in 79% of the cases while only 6% had anti-PVB19 IgM antibodies. PVB19 DNA presence was associated with seropositivity for anti-PVB19 IgG (P < 0.05) but not with IgM antibodies, indicating subclinical activation of latent infection. No correlation was found between the presence of PVB19 DNA and a patient's age, sex, type of psoriasis, or psoriasis area and severity index. The data demonstrated a statistically significant association between psoriasis and PVB19. Therefore, we suggest that PVB19 infection may be of pathophysiological importance in psoriasis.

The changes in expression of ICAM-3, Ki-67, PCNA, and CD31 in psoriatic lesions before and after methotrexate treatment.

Although the effectiveness of methotrexate (MTX) in the treatment of psoriasis is very well established, the mechanism of action is poorly understood. It was suggested that the therapeutic effect of MTX in psoriasis might be mediated by inhibition of adhesion molecule expression. The aim of our study was to investigate the different effects of MTX treatment on cell proliferation, inflammatory infiltrate, adhesion molecules, and angiogenesis in psoriasis, and to clarify the mechanism by which MTX exerts its therapeutic effects. Clinical response, the morpho-phenotypic changes, epidermal thickness, and mitosis count were analyzed and the expression of CD31 and ICAM-3, proliferative markers such as Ki-67, PCNA, were evaluated by immunohistochemical techniques in lesional psoriatic epidermis, before and after the treatment with MTX in ten patients. In posttreatment biopsies a decrease in the degree of epidermal hyperplasia and a significant reduction in the severity of the inflammatory infiltrate (P<0.05) were observed. In addition, CD31 and ICAM-3 expression was significantly decreased on dermal cellular infiltrate, (respectively; P<0.05, P<0.01). Ki67 and PCNA expression were suppressed concurrently in about 90% of cases (P<0.01). We suggest that MTX may have an inhibitory effect on an initial integral component of the pathways that lead to psoriasis. Immunopharmacologic intervention in adhesion event has the potential to improve psoriasis. Inhibition of revascularization may be another mechanism of action of MTX.

Treatment of lichen planopilaris with mycophenolate mofetil.

Mycophenolate mofetil (MMF) is an immunosuppressive drug that has recently been used to treat autoimmune and inflammatory skin diseases. We report the first case of lichen planopilaris (LPP) successfully treated with MMF. The treatment of our patient demonstrates a novel therapeutic option for patients with LPP; MMF treatment may be preferable to azathioprine treatment because MMF has a safer adverse-effect profile. Larger studies must be performed to establish the risk-benefit ratio of various therapeutic dosages of MMF for these patients.

Oxidant / antioxidant status in patients with psoriasis.

Psoriasis is a common, chronic inflammatory skin disease with unknown etiology. Recently it has been suggested that increased ROS production and deficient function of antioxidant systems activities may be involved in the pathogenesis of the disease. Although there are several studies investigating oxidant/antioxidant systems in psoriatic patients, the data obtained from these studies is not concordant. In this study, superoxide dismutase (SOD) enzyme activity, and malondialdehyde (MDA) and antioxidant potential (AOP) levels in thirty-five patients with psoriasis were investigated and compared with those of twenty-four control subjects. Clinical severity of the disease was determined according to the Psoriasis Area and Severity Index (PASI) scores in the patients. Plasma SOD activity and MDA levels were significantly higher (p=0.012 and p=0.005 respectively), whereas AOP levels were lower, in patients than controls (p=0.001). There was no correlation between PASI scores and plasma SOD, MDA, and AOP levels. Our findings may provide some evidence for a potential role of increased ROS production and decreased antioxidant activity in psoriasis.