RESUMEN
The catechol-O-methyl transferase (COMT) 158Val/Met variant has been suggested to play a role in COMT function. Epigenetic regulation of COMT may further influence the prevalence of metabolic syndrome in these patient populations. This study examined the correlation between COMT promoter methylation and metabolic syndrome in schizophrenia patients receiving atypical antipsychotic (AAP) therapy. DNA was extracted from peripheral blood samples of schizophrenia subjects screened for metabolic syndrome. Pyrosequencing was used to analyze two methylation sites of the soluble COMT (COMT-s) promoter region. Associations between AAP use, lifestyle variables, metabolic syndrome and COMT genotype with peak methylation values were analyzed. Data are reported in 85 subjects. Methylation on CpG site 1 had a mean of 79.08% (±4.71) and it was 12.43% (±1.19) on site 2. COMT genotype proved to be an indicator of COMT methylation status on site 1 (F(2, 84)=5.78, P=0.0044) and site 2 (F(2, 84),=3.79, P=0.027). A significant negative correlation between physical activity and COMT promoter region methylation was found in Val/Val homozygous patients (site 1: P=0.013 and site 2: P=0.019). Those homozygous for Met/Met showed a positive correlation between promoter site methylation and physical activity (site 1: P=0.027, site 2: P=0.005), and between CpG site methylation and metabolic syndrome (site 1: P=0.002; site 2: P=0.001). The results of this study suggest that COMT promoter region methylation is largely influenced by COMT genotype and that physical activity plays a significant role in epigenetic modulation of COMT.
Asunto(s)
Antipsicóticos/administración & dosificación , Catecol O-Metiltransferasa/genética , Síndrome Metabólico/genética , Esquizofrenia/genética , Adulto , Anciano , Islas de CpG/genética , Metilación de ADN/genética , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Actividad Motora , Regiones Promotoras Genéticas , Esquizofrenia/complicaciones , Esquizofrenia/patologíaRESUMEN
INTRODUCTION: The brain-derived neurotrophic factor (BDNF) Val66Met variant and HMG-COA reductase inhibitors (statins) have been implicated in insulin resistance with a possible increased risk of diabetes. We sought to determine the effect of the BDNF Met variant and statin medication use on insulin resistance in schizophrenia and bipolar disorder using the homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: A cross-sectional design was used and patients with diabetes or on any medications affecting glucose regulation were -excluded. Associations between insulin resistance and genotype were then analyzed by ANOVA and regression analysis. Subjects were grouped by BDNF genotype as well as presence of statin. RESULTS: Two hundred fifty-two subjects with a mean age of 44 years were included. The group was 53% male and 41% had a diagnosis of bipolar disorder; 78% and 19% were receiving atypical antipsychotics (AAPs) and statin medications, respectively. Analysis showed schizophrenia subjects with the BDNF met allele as well as schizophrenia subjects with both the BDNF met allele and were receiving a statin had significantly higher HOMA-IR values compared to the other groups (p= 0.046 and p= 0.016, respectively). CONCLUSIONS: Our results suggest that in the metabolically high-risk population of schizophrenia the BDNF met allele alone and in combination with statin medications is associated with higher insulin resistance values. This was not seen in the bipolar population. Further validation of these associations remains necessary.
Asunto(s)
Trastorno Bipolar/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Predisposición Genética a la Enfermedad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Resistencia a la Insulina/genética , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genética , Adulto , Sustitución de Aminoácidos/genética , Demografía , Femenino , Heterocigoto , Humanos , MasculinoRESUMEN
Bacillus stearothermophilus BR219, a phenol-resistant thermophile, can convert phenol to the specialty chemical catechol. The growth kinetics of this organism were studied in batch, continuous, and immobilized-cell culture. Batch growth was insensitive to pH between 6.0 and 8.0, but little growth occurred at 5.5. In continuous culture on a dilute medium supplemented with 10 mM phenol, several steady states were achieved between dilution rates of 0.25 and 1.3 h-1. Phenol degradation was found to be uncoupled from growth. Immobilized cells grew rapidly in a rich medium, but cell viability plummeted following a switch to a dilute medium supplemented with 5 mM phenol.