RESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is mainly caused by deletions in SMA-related genes. The objective of this study was to develop gene-dosage assays for diagnosing SMA. METHODS: A multiplex, quantitative PCR assay and a CNVplex assay were developed for determining the copy number of SMN1, SMN2, and NAIP. Reproducibility and specificity of the two assays were compared to a multiple ligation-dependent probe amplification (MLPA) assay. To evaluate reproducibility, 30 samples were analyzed three times using the three assays. A total of 317 samples were used to assess the specificity of the two assays. RESULTS: The multiplex quantitative PCR (qPCR) assay had higher reproducibility. Intra-assay CVs were 3.01%-8.52% and inter-assay CVs were 4.12%-6.24%. The CNVplex assay had ratios that were closer to expected (0.49-0.5 for one copy, 1.03-1.0 for two copies, and 1.50-1.50 for three copies). Diagnostic accuracy rates for the two assays were 100%. CONCLUSIONS: The multiplex qPCR assay was a simple, rapid, and cost-effective method for routine SMA diagnosis and carrier screening. The CNVplex assay could be used to detect SMAs with complicated gene structures. The assays were reliable and could be used as alternative methods for clinical diagnosis of SMA.
Assuntos
Variações do Número de Cópias de DNA/genética , Marcadores Genéticos/genética , Atrofia Muscular Espinal/diagnóstico , Proteína Inibidora de Apoptose Neuronal/genética , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Genótipo , Humanos , Reação em Cadeia da Polimerase Multiplex , Atrofia Muscular Espinal/genética , Reprodutibilidade dos Testes , Deleção de Sequência , Proteína 2 de Sobrevivência do Neurônio Motor/genéticaRESUMO
Tacrolimus is a widely used immunosuppressive drug for preventing the rejection of solid organ transplants. The efficacy of tacrolimus shows considerable variability, which might be related to genetic variation among recipients. We conducted a retrospective study of 240 Chinese renal transplant recipients receiving tacrolimus as immunosuppressive drug. The retrospective data of all patients were collected for 40 days after transplantation. Seventeen SNPs of CYP3A5, CYP3A4, COMT, IL-10 and POR were identified by the SNaPshot assay. Tacrolimus blood concentrations were obtained on days 1-3, days 6-8 and days 12-14 after transplantation, as well as during the period of the predefined therapeutic concentration range. Kruskal-Wallis test was used to examine the effect of genetic variation on the tacrolimus concentration/dose ratio (C 0/D) at different time points. Chi-square test was used to compare the proportions of patients who achieved the target C 0 range in the different genotypic groups at weeks 1, 2, 3 and 4 after transplantation. After correction for multiple testing, there was a significant association of C 0/D with CYP3A5*3, CYP3A4*1G and CYP3A4 rs4646437 T>C at different time points after transplantation. The proportion of patients in the IL-10 rs1800871-TT group who achieved the target C 0 range was greater (pâ=â0.004) compared to the IL-10 rs1800871-CT and IL-10 rs1800871-CC groups at week 3 after transplantation. CYP3A5*3, CYP3A4 *1G, CYP3A4 rs4646437 T>C and IL-10 rs1800871 C>T might be potential polymorphisms affecting the interindividual variability in tacrolimus metabolism among Chinese renal transplant recipients.
Assuntos
Catecol O-Metiltransferase/genética , Citocromo P-450 CYP3A/genética , Interleucina-10/genética , NADPH-Ferri-Hemoproteína Redutase/genética , Polimorfismo de Nucleotídeo Único/genética , Tacrolimo/metabolismo , Adulto , Povo Asiático/genética , Feminino , Humanos , Imunossupressores/metabolismo , Imunossupressores/farmacologia , Transplante de Rim , Masculino , Estudos Retrospectivos , Tacrolimo/farmacologiaRESUMO
OBJECTIVE: To analyze the causes of death and potential years of life lost (PYLL) in 7 districts of Guangzhou from 2003 to 2005. METHODS: The bureau of Health of Guangzhou provided the data of 70 201 cases of death occurring between 2003 and 2005. The top 10 causes of death were analyzed and the PYLL and crude death rate were calculated using mortality difference dissembling method. RESULTS: Between 2003 and 2005, the top 3 causes of death in Guangzhou were diseases of the circulatory system, neoplasms and respiratory diseases. Aging of the population led to an increased death rate. The major causes of death affecting PYLL consisted of neoplasms, diseases of the circulatory system, injuries and poisoning. CONCLUSION: Priority should be given to the control of diseases of the circulatory system in the health care in Guangzhou. Neoplasms, injuries and poisoning all contribute to a high PYLL.