RESUMEN
BACKGROUND: Abnormal expressions of the N-methyl-D-aspartate receptor and its interacting postsynaptic density (PSD) molecules have been hypothesized to be involved in the pathophysiology of schizophrenia. Few studies have carried out association studies with DLG4 gene (coding PSD-95 protein) and sought to validate the results with Asian schizophrenia patients. PATIENTS AND METHODS: To further investigate the significance of DLG4 in Asian schizophrenic patients, we examined seven single-nucleotide polymorphisms (SNPs) within this gene in 1504 unrelated Chinese mainland individuals (893 patients and 611 controls). RESULTS: No association was found between these seven SNPs and schizophrenia within our sample. No significant differences in allele or genotype frequencies between schizophrenic paranoid patients and controls were found. CONCLUSION: Although no allelic or genotypic variances of this gene were observed, the possibility that SNPs within DLG4 represent a positive schizophrenia risk gene cannot be excluded. Our research provided a reference for further research into this gene in other populations.
Asunto(s)
Pueblo Asiatico/genética , Etnicidad/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genética , Adulto , Alelos , Homólogo 4 de la Proteína Discs Large , Femenino , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Persona de Mediana EdadRESUMEN
A total of 130 Chinese schizophrenic patients (45 male, 85 female) were enrolled in the study. Clinical efficacy was determined using Brief Psychiatric Rating Scale (BPRS) scores. We genotyped 10 single-nucleotide polymorphisms (SNPs) of the catechol-O-methyl transferase gene (COMT) in our patients and re-examined them for association with changes in BPRS scores after 8 weeks of risperidone monotherapy. COMT is one of the genes that confer susceptibility to schizophrenia, both because of its role in neurotransmitter metabolism and because of its location in the high-risk schizophrenia-related region 22q11. Recent studies also found that COMT functional polymorphisms influenced individual response to antipsychotic medication. Our aim in this study was to explore the influence of COMT polymorphisms on pharmacological response to risperidone in the Chinese population. Statistical analysis revealed a significant association between an upstream COMT SNP, rs9606186, and scores reduction of BPRS in all patients and in the male subgroup but not in the female subgroup (allele analysis: P=0.055 for all, P=0.012 for male patients; genotype analysis: P=0.046 for all, P=0.020 for male patients, uncorrected, odds ratio=3.95). The COMT gene polymorphism, SNP rs9606186, is associated with risperidone therapy efficiency in the Chinese population. This association exhibited a sexually dimorphic difference, which may shed light on the genetics of COMT and its enzymatic sex-dependent mechanism.
Asunto(s)
Antipsicóticos/uso terapéutico , Catecol O-Metiltransferasa/genética , Farmacogenética , Polimorfismo de Nucleótido Simple , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Femenino , Humanos , Masculino , Esquizofrenia/genéticaRESUMEN
Colorectal cancer (CRC), now the third most common cancer across the world, is known to aggregate in families. USP7 is a very important protein with an important role in regulating the p53 pathway, which is critical for genomic stability and tumor suppression. We here genotyped eight SNPs within the USP7 gene and conducted a case-control study in 312 CRC patients and 270 healthy subjects in the Chinese Han population. No significant associations were found for any single SNP and CRC risk. Our data eliminate USP7 as a potential candidate gene towards for CRC in the Han Chinese population.
