Sterol 14alpha-demethylase (CYP51), the most widely distributed member of the P450 superfamily, is the key enzyme in sterol biosynthesis pathway. CYP51 is not only an important model for fundamental P450 structure/function studies, but also an important target protein of cholesterol-lowering agents, antifungal drugs and herbicides. This article reviewed the research advances in CYP51 at various aspects, including sequence characteristics, physiological roles, catalytic properties in vitro, protein structure, structure-function relationships and inhibition of CYP51. The problems remained in current research and designations of CYP51 inhibitors are also discussed.
Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; genetics ; physiology ; Mutagenesis, Site-Directed ; Sequence Analysis, Protein ; Sterol 14-Demethylase

Objective To investigate the association between TGFβ1-509 C/T gene polymorphism with primary ANCA associated vasculitis (AAV) in Chinese Han population . Methods The blood DNA and clinical data of 88 patients were collected, TGFβ1-509 C/T genotypes were determined by PCR-RFLP, 107 healthy individuals were tested as controL Clinical and pathological data of the patients with different genotype were compared. Results No significant difference was found in neither genotype distributions nor allele frequencies between the patients and the control (P > 0. 05). Significant difference was found in uria protien level of the three groups of patients with different genotypes(P <0.05) ,but not in blood pressure, serum urea nitrogen or creatinine, vasculitic damage index, birminghan vasculitis activity score (P > 0. 05 ). Significant difference was found in med-heavier glomerular mesangial proliferation of the three groups ( P < 0.05 ) , but not in lighter glomerular mesangial proliferation, glomerular sclerosis, crescent formation and tubule-interstitial fibrosis and atrophy. Conclusions In Chinese Han population, TGFβ1-509 C/T polymorphism might have no relationship to susceptibility of primary AAV, but might relate to uria protein and med-heavier degree of mesenterium proliferation.

Objective To investigate the relationship between TGFβ1-509 C/T, TCRCα-575 A/G SNPs and primary AAV using a transmission disequilibrium theory based pedigree analysis Methods Genotypes of 264 individuals from 88 AAV families include patients, their parents, brothers and sisters were determined by PCR-RFLP and direct sequencing. Transmission disequilibrium test(TDT) and HRR were employed for the data analysis to observe the transmission disequilibrium of TGF31-509 C/T and TCRCα -575 A/G polymorphisms. Results No transmission disequilibrium from heterozygous parents onto the patients was found in the trios analyzed by TDT for either TGFβ1-509 C/T (observed C/T = 36/28, expected C/T =33. 5/30. 5, x2 =0.51, P＞0.05) or TCRCo-575 A/G ( observed A/G = 29/39, expected A/G = 33.5/34. 5, x2 = 1. 59, P ＞ 0. 05 ). The genotype-based HRR and haplotype-based HRR showed there was no increased risk of AAV in the observed trios for either -509 C/T polymorphism of TGFβ1 (transmitted genotype CC/CT/TT =12/20/6, allele C/T = 44/32; nontransmitted genotype CC/CT/TT = 10/19/9,allele C/T =39/37, genotype-based HRR x2 =0.81, P ＞0. 05, haplotype-based HRR x2 =0. 66, P＞0. 05,HRR = 1.30) or -575 A/G polymorphism of TCRCα ( transmitted genotype AA/AG/GG = 9/18/12, allel A/G = 36/42; nontransmitted genotype AA/AG/GG = 15/15/9, allel A/G = 35/33, genotype-based HRR x2=2. 20, P ＞0. 05. Haplotype-based HRR x2 =0. 41, P ＞0. 05, HRR =0. 81 ). The deviation of HRR coefficient was not excessive(1.00). Conclusion TGFβ1-509 C/T and TCRCo-575 A/G polymorphism may not be associated with the genetic susceptibility of primary AAV in Guangxi Han population.

PURPOSE: Effective biomarkers and models are needed to improve the prognostic prospects of clear cell renal cell carcinoma (ccRCC). The purpose of this work was to identify DNA methylation biomarkers and to evaluate the utility of DNA methylation analysis for ccRCC prognosis. MATERIALS AND METHODS: An overview of genome-wide methylation of ccRCC tissues derived from The Cancer Genome Atlas (TCGA) database was download for analysis. DNA methylation signatures were identified using Cox regression methods. The potential clinical significance of methylation biomarkers acting as a novel prognostic markers was analyzed using the Kaplan-Meier method and receiver operating characteristic (ROC) curves. RESULTS: This study analyzed data for 215 patients with information on 23171 DNA methylation sites and identified a two-DNA methylation signature (cg18034859, cg24199834) with the help of a step-wise multivariable Cox regression model. The area under the curve of ROCs for the two-DNA methylation signature was 0.819. The study samples were stratified into low- and high-risk classifications based on an optimal threshold, and the two groups showed markedly different survival rates. Moreover, the two-DNA methylation marker was suitable for patients of varying ages, sex, stages (I and IV), and histologic grade (G2). CONCLUSION: The two-DNA methylation signature was deemed to be a potential novel prognostic biomarker of use in increasing the accuracy of predicting overall survival of ccRCC patients.
Biomarkers ; Carcinoma, Renal Cell ; Classification ; DNA Methylation ; Genome ; Humans ; Methods ; Methylation ; Prognosis ; ROC Curve ; Survival Rate

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome