Assuntos
Dieta Cetogênica , Dieta Vegetariana , Disbiose/dietoterapia , Obesidade Abdominal/dietoterapia , Obesidade Abdominal/epidemiologia , Redução de Peso , Adolescente , Adulto , Idoso , Animais , Índice de Massa Corporal , Criança , Impedância Elétrica , Feminino , Microbioma Gastrointestinal , Humanos , Inflamação/dietoterapia , Masculino , Camundongos , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
BACKGROUND: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by ATP7B pathogenic mutations. The symptoms of WD can be effectively prevented if the affected individuals are identified and intervened early. However, clinical utility of this molecular analysis is challenging due to hundreds of variants with various clinical effects in the gene. Here, we aim to describe the spectrum of ATP7B variants and assess their clinical effects in the Han Chinese population. METHODS: The ATP7B gene was directly sequenced in 632 unrelated WD patients and 503 unrelated healthy individuals. The effects of identified variants were classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Different frequency of variants observed in both cases and controls were tested using Chi-square or Fisher's exact tests. RESULTS: We detected 161 non-synonymous variants in these 632 WD patients, 58 of which were novel. Among these variants, 78, 64, 8, 4, and 7 were classified as 'pathogenic variants', 'likely pathogenic variants', 'variants with uncertain significance', 'likely benign variants', and 'benign variants', respectively. Ninety percent (569/632) of these WD patients can be genetically diagnosed with two or more 'pathogenic' or 'likely pathogenic' variants. The 14 most common disease-causing variants were found at least once in 94% (537/569) of genetically diagnosed patients. CONCLUSIONS: These data expand the spectrum of ATP7B variants and facilitate effective screening for ATP7B variants for early diagnosis of WD and development of individualized treatment regimens.
Assuntos
Adenosina Trifosfatases/genética , Proteínas de Transporte de Cátions/genética , Variação Genética , Genótipo , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , Povo Asiático , ATPases Transportadoras de Cobre , Frequência do Gene , Testes Genéticos , Humanos , Análise de Sequência de DNARESUMO
The apoptotic pathway is important in the control of vital processes of hepatocellular carcinoma (HCC). In the current study, we aimed to determine whether apoptotic gene-related polymorphisms modified HCC prognosis. We genotyped 16 single nucleotide polymorphisms (SNPs) in 10 core genes (TP53, TP53INP1, TP53BP1, CDKN2A, CDKN1A, CDKN1B, MDM2, BAX, CCDN1 and BCL2) in the apoptotic pathway by using DNA from blood samples of 362 HCC patients receiving surgical resection of HCC tumor. The associations between genotypes/haplotypes of the 10 genes and overall survival (OS) of HCC patients were assessed using the Cox proportional hazards model. We found one CDKN1B haplotype CCT/ACT (constructed by rs36228499 C>A, rs34330 C>T and rs2066827 T>G) significantly associated with decreased OS of HCC patients, compared to the common haplotype ACT/CTT both in univariate analysis (P=0.013, HR=1.198, 95% CI: 1.039-1.381) and multivariate analysis (P=0.006, HR=1.224, 95% CI: 1.059-1.413). We also find two SNPs (rs560191 G>C and rs2602141 T>G) in TP53BP1 shown to be marginally significantly associated with decreased OS of HCC patients. However, none of the other SNPs or haplotypes were significantly associated with HCC OS. Our results illustrated the potential use of CDKN1B haplotype as a prognostic marker for HCC patients with surgical resection of tumor.
