Association between interleukin-17F rs763780 polymorphism and psoriasis risk: A meta-analysis.

BACKGROUND: The polymorphism of interleukin-17F rs763780 has been found to have a probable association with increased risk of developing psoriasis. AIMS: This study aims to get a more convincing estimation of the association between the interleukin-17F rs763780 T /C polymorphism and psoriasis risk. METHODS: Two authors independently searched the databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Wanfang and Chinese Biomedical Literature Databases for case-control studies which reported the odds ratios with 95% confidence intervals comparing genotype and allele frequencies of the interleukin-17F rs763780 polymorphism in patients with psoriasis versus participants without psoriasis. RESULTS: A total of seven case-control studies incorporating 1824 cases and 1585 controls were identified. The pooled odds ratios indicated that interleukin-17F rs763780 C allele was a risk factor for psoriasis in allele frequency, recessive model and homozygote model (P < 0.05). Subgroup analysis by ethnicity further indicated that the C allele was closely related to increased risk of psoriasis in Asian populations (P < 0.05), but not in Caucasians. LIMITATIONS: Only a few studies on the interleukin-17F rs763780 polymorphism in psoriasis have been reported till date, thus the data is insufficient. Only one gene polymorphic site was selected for this study, and it is not clear whether other genetic mutation functional sites affect the gene. Further studies on confounding effects of other genetic polymorphisms are needed. CONCLUSION: The present meta-analysis results suggested that the interleukin-17F rs763780 T /C is significantly associated with psoriasis risk in Asians.

Associations between vitamin D receptor gene polymorphisms and chronic spontaneous urticaria in Chinese Han population.

INTRODUCTION: Previous studies found that vitamin D receptor (VDR) TaqI, BsmI, FokI and ApaI gene polymorphisms are associated with several inflammatory diseases. However, the relationship between VDR gene polymorphisms and chronic spontaneous urticaria (CSU) is not clear. AIM: The purpose of our study was to explore the relationship between the polymorphism of VDR and the incidence of chronic spontaneous urticaria in the Chinese Han population. Meanwhile, the vitamin D levels in patients with chronic spontaneous urticaria were also detected and the effects of VDR gene polymorphism on vitamin D levels were detected. MATERIAL AND METHODS: The genotypes of four VDR polymorphisms (TaqI, BsmI, ApaI, and FokI) were studied using allele-specific PCR analysis in 90 CSU patients and 90 healthy controls. RESULTS: Compared to the control group, the mutant allele (C) of FokI were more common in patients with CSU (57.2% vs. 45%, p = 0.020, odds ratio (OR) = 0.612, 95% confidence interval (CI): 0.403-0.928). We found that serum vitamin D levels were significantly lower in CSU patients than in healthy controls (p = 0.023). However, the effect of VDR gene polymorphism on vitamin D levels was not found in patients of CSU. CONCLUSIONS: We first reported the effect of VDR gene FokI (rs2228570) polymorphism on the incidence of chronic spontaneous urticaria in the Chinese Han population.

Etanercept biosimilar (recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein) and methotrexate combination therapy in Chinese patients with moderate-to-severe plaque psoriasis: a multicentre, randomized, double-blind, placebo-controlled trial.

Etanercept biosimilar recombinant human tumour necrosis factor-α receptor II: IgG Fc fusion protein (rhTNFR-Fc, trade name Yisaipu) has shown good efficacy in the treatment of moderate-to-severe plaque psoriasis. To compare the efficacy and safety of rhTNFR-Fc plus methotrexate (MTX) and rhTNFR-Fc plus placebo in Chinese patients with moderate-to-severe plaque psoriasis. In this multicentre, randomized, placebo-controlled trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned in a 1:1 ratio to receive rhTNFR-Fc plus MTX or rhTNFR-Fc plus placebo. The primary endpoint was the proportion of patients achieving Psoriasis Area and Severity Index improvement of at least 75% (PASI 75) from baseline at week 24. Adverse events (AEs) were recorded to evaluate safety. Efficacy analysis was performed using the intent-to-treat principle. A total of 466 patients were enrolled and randomly received rhTNFR-Fc plus MTX (combination group, n = 233) or rhTNFR-Fc plus placebo (monotherapy group, n = 233). PASI 75 at week 24 was significantly higher in the combination group than in the monotherapy group (81.86% vs. 65.50%, p < 0.001). Similar results were observed in other PASI improvement scores at week 12 [PASI 75, 62.39% vs. 44.54% (p < 0.001); PASI 50, 87.17% vs. 75.55% (p = 0.001); and PASI 90, 34.07% vs. 18.78% (p < 0.001)] and week 24 [PASI 50, 92.48% vs. 85.59% (p = 0.019); and PASI 90, 64.16% vs. 42.36% (p < 0.001)]. Significantly more patients had a static Physicians' Global Assessment of clear or almost clear in the combination group than in the monotherapy group at week 12 (26.46% vs. 12.50%, p < 0.001) and week 24 (62.38% vs. 40.83%, p < 0.001). The most common AEs in the two groups were upper respiratory tract infection and abnormal liver function. The combination therapy of rhTNFR-Fc plus MTX was an effective therapy for moderate-to-severe plaque psoriasis with an acceptable safety and tolerability profile, indicating that it was feasible and well tolerated for patients.

[Analysis of ADAR1 gene mutation in a pedigree affected with dyschromatosis symmetrical hereditaria].

OBJECTIVE: To detect mutation of adenosine deaminase acting on RNA1 (ADAR1) gene in a pedigree affected with dyschromatosis symmetrical hereditaria (DSH). METHODS: Clinical data and peripheral blood samples of the patients from the pedigree were collected. Potential mutations of the ADAR1 gene were screened among 2 patients, 2 unaffected individual from the pedigree as well as 50 unrelated healthy controls by PCR amplification and direct sequencing. RESULTS: A c.3463C>T (p.R1155W) missense mutation of the ADAR gene was identified in the 2 patients, which was absent in the 2 healthy relatives and 50 unrelated controls. The mutation has been previously identified among 5 Chinese families and was the most common mutation site. CONCLUSION: The c.3463C>T missense mutation of the ADAR gene probably underlies the disease in this pedigree.

MicroRNA-21 regulates the ERK/NF-κB signaling pathway to affect the proliferation, migration, and apoptosis of human melanoma A375 cells by targeting SPRY1, PDCD4, and PTEN.

This study aims to explore the effects of microRNA-21 (miR-21) and ERK/NF-κB signaling pathway on human melanoma A375 cells. The melanoma tissues and adjacent normal tissues were obtained from 45 melanoma patients. qRT-PCR was conducted to quantify the expression of miR-21 and the gene mRNA expressions. Human melanoma A375 cells were divided into the Mock, negative control (NC), miR-21 inhibitors, miR-21 inhibitors + siRNA-SPRY1, miR-21 inhibitors + siRNA-PDCD4, and miR-21 inhibitors + siRNA-PTEN groups. Western blotting was used to determine protein expressions. CCK8 assay and Transwell assay were performed to evaluate the proliferation, migration, and invasion of A375 cells. Annexin V/propidium iodide double staining was adopted to detect cell apoptosis. MiR-21 expression was higher in melanoma tissues than in adjacent tissues, while the mRNA and protein expressions of SPRY1, PDCD4, and PTEN were lower in melanoma tissues than in adjacent tissues. Compared with the Mock and NC groups, the miR-21 inhibitors group exhibited increased expressions of SPRY1, PDCD4, and PTEN and decreased expressions of ERK, p-ERK, NF-κB p65, and p-NF-κB p65. After transfection of miR-21 inhibitors, the proliferation, migration, and invasion of A375 cells were inhibited, while the apoptosis of A375 cells was promoted. However, the effects of miR-21 inhibitors on the growth, migration, invasion, and apoptosis of A375 cells were reversed after transfection of siRNA-SPRY1, siRNA-PDCD4, or siRNA-PTEN. MiR-21 can promote the proliferation, migration, and inhibit the apoptosis of human melanoma A375 cells by inhibiting SPRY1, PDCD4, and PTEN via ERK/NF-κB signaling pathway. © 2016 Wiley Periodicals, Inc.

Hypermethylation of HLA-C may be an epigenetic marker in psoriasis.

BACKGROUND: There are no published studies that describe the DNA methylation of human leukocyte antigen class I molecules in psoriasis despite the fact that their association to disease has been known for several decades. OBJECTIVE: we investigated the methylation status of HLA-A, -B and -C loci in psoriatic epidermis. METHODS: The DNA and RNA specimens were obtained from the involved and uninvoled epidermis of 56 patients with plaque psoriasis and 28 healthy persons as the control group. Methylation of HLA was examined by MSP and Bisulfite sequencing. HLA-C mRNA expression was examined by Q-PCR. The severity of disease was evaluated by psoriasis area and severity index (PASI). RESULTS: In psoriatic lesions and psoriatic non-lesions, the percentage of promoter methylation for HLA-B was 3.57% (2/56) and 3.57% (2/56), while it was 14.28% (8/56) and 23.21% (13/56) for HLA-C, respectively. Methylation of HLA-A was not be detected in both psoriatic lesions and non-lesions. Methylation of HLA-A, -B and -C loci was not found in healthy controls. The frequency of promoter methylation for HLA-C in the psoriatic epidermis was significantly increased compared with healthy controls (p<0.05). Interestingly, there was no significant difference in HLA-C methylation between psoriatic lesions and non-lesions (χ(2)=1.465, p=0.167), which was further confirmed by using bisulfite sequencing (t=1.958, p=0.055). HLA-C methylation was not found in healthy controls. The mean methylation rate of HLA-C in psoriatic lesions is relative to PASI score (r=0.316, p=0.018). The mean methylation rate of HLA-C in psoriatic lesions and non-lesions of the patients (onset age ≤18 years) are higher than the other patients, respectively (t=6.884, p<0.001; t=6.551, p<0.001). The mean HLA-C mRNA expression was significantly higher in psoriatic non-lesions than normal skin (t=2.895, p=0.005), while there is no significant difference between psoriatic lesions and non-lesions (t=1.966, p=0.054). The mean value of HLA-C mRNA expression is not relative to the promoter methylation of HLA-C in psoriatic lesions and non-lesions, respectively. CONCLUSIONS: We first demonstrate hypermethylation of HLA-C gene in psoriatic epidermis, suggesting that HLA-C hypermethylation may be an epigenetic marker in psoriasis.

Calcipotriol plus betamethasone dipropionate gel compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized, controlled trial investigating efficacy and safety in a Chinese population.

BACKGROUND: Calcipotriol/betamethasone dipropionate combination in a non-alcoholic, lipophilic gel formulation (two-compound gel) has previously been demonstrated as a safe and effective treatment for scalp psoriasis in Caucasian, Hispanic/Latino, and Black/African American populations. The purpose of this randomized, investigator-blinded, active-controlled, 4-week study was to evaluate the efficacy and safety of the two-compound gel in Chinese subjects with scalp psoriasis. METHOD: Subjects were randomized in a 1 : 1 ratio to four weeks of treatment with either the two-compound gel once daily or calcipotriol scalp solution twice daily. Subjects were evaluated after one, two, and four weeks of treatment. The primary efficacy endpoint was the proportion of subjects who achieved "controlled disease" defined as "clear" or "minimal" disease according to investigator's global assessment of disease severity at week 4. RESULTS: The proportion of subjects who achieved "controlled disease" at week 4 was statistically significantly higher in the two-compound gel group (87.5%) than in the calcipotriol solution group (50.8%), (P < 0.0001). Greater and more rapid improvements with the two-compound gel were also observed in clinical signs (redness, thickness, and scaliness) and itching. The two-compound gel was associated with fewer adverse drug reactions than calcipotriol scalp solution (18.6% vs. 33.1%) (P = 0.011). CONCLUSIONS: The calcipotriol/betamethasone dipropionate gel applied once daily was significantly more effective and better tolerated than calcipotriol scalp solution applied twice daily in the treatment of scalp psoriasis over four weeks in Chinese subjects.

Cutaneous tuberculosis: a diagnostic and therapeutic study of 20 cases.

Cutaneous tuberculosis is showing a resurgence. It continues to be one of the most elusive and difficult diseases to diagnose in dermatological practice. We sought to describe the clinical manifestations, laboratory features, and antituberculous therapy in cases of cutaneous tuberculosis. Twenty cases of cutaneous tuberculosis were observed in this study. Of the 20 cases, seven were in women (35%) and 13 were in men (65%). There were eight (40%) cases of lupus vulgaris, four (20%) cases of orificial tuberculosis, four (20%) cases of tuberculosis verrucosa cutis, two (10%) cases of scrofuloderma, and two (10%) cases of primary inoculation tuberculosis. In total, 20 strains of acid-fast bacilli were isolated by culture in Löwenstein-Jensen medium at 37°C. Mycobacterial species identification by polymerase chain reaction (PCR) assay showed that all strains were Mycobacterium tuberculosis. In vitro susceptibility testing by use of absolute concentration method showed that the 20 strains were sensitive to rifampin, ethambutol, and isoniazid; however, two strains were resistant to streptomycin. All of the patients responded favourably to antituberculous treatment. Cutaneous tuberculosis is a skin disease that should still be thought much of in mainland China, and in this study lupus vulgaris is the most common clinical presentation.

Two new mutations of the ADAR1 gene associated with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. Genetic studies have identified mutations in ADAR1 gene to be responsible for this disorder. We detected two mutations in two families with DSH, which include a heterozygous g-->a transversion at the first base of the 3'-acceptor splice site of intron 5 (c. 2080-1g>a, IVS5-1g>a) and a transition c.3076C>T. IVS5-1g>a should prevent proper splicing of the transcript while c.3076C>T leading to a missense mutation p.R1026W of the ADAR1 gene. Our study suggests that splice site mutation IVS5-1g>a and missense mutation p.R1026W are new mutations of ADAR1 gene, which should be useful in genetic counseling and prenatal diagnosis for the affected families and expanding the database on ADAR1 gene mutations in DSH.

[The methylation locus and frequency pattern on p16 INK4a gene promoter CpG in epidermis of patients with psoriasis].

OBJECTIVE: To investigate the CpG methylation locus and frequency pattern on p16 INK4a gene promoter in epidermis of p16 INK4a methylated patients with psoriasis vulgaris. METHODS: The DNA specimens were obtained from epidermal lesion of 50 plaque psoriatic patients. Methylation specific PCR and DNA sequencing were used to detect the frequency and locus of methylation in p16 INK4a gene promoter region. RESULTS: Approximately 50% CpG was methylated in p16 INK4a methylated patients, methylation was found in specifical locus of p16 INK4a gene promoter. CONCLUSION: The distinct methylation pattern is showed on the p16 INK4a gene promoter region in patients with psoriasis.