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Psoriasis is characterized by hyperproliferation and abnormal differentiation of keratinocytes, and inflammation. 1,25-Dihydroxyvitamin D3, which is used for the treatment of psoriasis, binds to vitamin D receptor (VDR) and modulates gene transcription. We analyzed VDR gene FokI, ApaI and TaqI polymorphisms in 51 Turkish familial psoriasis patients (psoriasis vulgaris and psoriatic arthritis) and 100 healthy subjects, and evaluated the correlation between VDR genotypes and calcipotriol response. We found that the TT genotype was significantly more frequent in the patients than in the controls (51 vs. 35%: P < or = 0.05). The frequency of the T allele in patients was also significantly higher than that in the controls (73.5 vs. 59.5%: P < or = 0.025). In psoriatic arthritis patients, T allele frequency was even higher (91.7%: P < or = 0.05). With regard to response to calcipotriol treatment, in nonresponsive patients TT genotype and T allele frequencies were higher than they were in the controls (63.6 vs. 35%: P < or = 0.025, 81.8 vs. 59.5%: P < or = 0.01, respectively). In conclusion, we show that VDR gene TaqI polymorphism is associated with familial psoriasis in the Turkish population. We also demonstrate that VDR gene polymorphisms may play a role in partial resistance to calcipotriol therapy.

Spinal muscular atrophy is an autosomal recessive motor neuron disease that is caused by mutation of the survival motor neuron gene (SMN1) but all patients retain a nearly identical copy, SMN2. The disease severity correlates inversely with increased SMN2 copy. Currently, the most promising therapeutic strategy for spinal muscular atrophy is induction of SMN2 gene expression by histone deacetylase inhibitors. Polyphenols are known for protection against oxidative stress and degenerative diseases. Among our candidate prodrug library, we found that (E )-resveratrol, which is one of the polyphenolic compounds, inhibited histone deacetylase activity in a concentration-dependent manner and half-maximum inhibition was observed at 650 microM. Molecular docking studies showed that (E )-resveratrol had more favorable free energy of binding (-9.09 kcal/mol) and inhibition constant values (0.219 microM) than known inhibitors. To evaluate the effect of (E )-resveratrol on SMN2 expression, spinal muscular atrophy type I fibroblast cell lines was treated with (E )-resveratrol. The level of full-length SMN2 mRNA and protein showed 1.2- to 1.3-fold increase after treatment with 100 microM (E )-resveratrol in only one cell line. These results indicate that response to (E )-resveratrol treatment is variable among cell lines. This data demonstrate a novel activity of (E )-resveratrol and that it could be a promising candidate for the treatment of spinal muscular atrophy.

The aim of this study is to evaluate the effects of estrogen receptor 1 (ESR1) and vitamin D receptor (VDR) gene polymorphisms on bone mineral density (BMD) in a group of previously untreated osteoporotic women. Effects of demographic, environmental, and hormonal factors were also evaluated in this context. Fifty women who did not have a prior diagnosis or treatment of osteoporosis were compared with 50 nonosteoporotic postmenopausal women. Demographic and morphometric characteristics, medical history, dietary habits, exercise history, and sunlight exposure were recorded. The diagnosis of osteoporosis was made with regard to BMD measurements with DEXA. Blood samples were obtained for serum biochemistry, bone turnover markers, and VDR and ESR1 gene polymorphism analysis. Polymorphic sites of VDR and ESR1 genes were amplified by polymerase chain reaction and examined using restriction fragment length polymorphism. Bb genotype was significantly higher in the osteoporotic group when compared to controls (p=0.022). Each 1 U decrease in the body mass index (BMI) increased the risk of osteoporosis by 8% independent of the genotype. We could not observe a significant effect of ESR1 polymorphism on BMD or osteoporosis risk. The interaction of ApaI and BsmI genotypes were found to be significant (p=0.041) and the AaBb genotype, when corrected for BMI, was shown to increase the risk of osteoporosis five times (p=0.005). However, the results demonstrated insignificant p values when correction for multiple testing was performed with the Bonferroni method in the logistic regression model. A predominance of Bb genotype of the VDR gene was evident in this group of postmenopausal Turkish women. Moreover, the combined genotype AaBb conferred a five times increased risk for osteoporosis when corrected for clinical variables.

IntroductionProximal spinal muscular atrophy (SMA) is a common autosomal recessively inherited neuromuscular disorder. It is caused by homozygous absence of the survival motor neuron 1 (SMN1) gene. SMN2, which modulates the severity of the disease, represents a major target for therapy. The aim of this study was to investigate whether SMN2 expression can be increased by caffeic acid, chlorogenic acid and curcumin, which are designed by modifications of the carboxylic acid class of histone deacetylase (HDAC) inhibitors.Material and methodsUsing quantitative real-time PCR, we analysed the levels of full-length SMN2 and Δ7SMN2 mRNA. We performed LDH cytotoxicity assay to analyse whether SMN2 activating concentrations of caffeic acid, chlorogenic acid and curcumin were cytotoxic to fibroblasts.ResultsWe found that caffeic acid and curcumin were more efficient than chlorogenic acid and increased full-length SMN2 mRNA levels 1.5 and 1.7-fold, respectively. Δ7SMN2 mRNA levels were measured to investigate alternative splicing of exon 7. We also found that cytotoxicity was not observed at SMN2 activating concentrations.ConclusionsOur data suggest that carboxylic acid derivatives including phenolic structure and symmetry could be a good candidate for SMA treatment.