RESUMO
OBJECTIVE: To identify novel polymorphisms in the genes encoding the transcription factors CCAAT/enhancer binding protein alpha, beta and delta ( CEBPA, CEBPB, CEBPD) and investigate associations between polymorphisms and obesity-related phenotypes. METHODS: Denaturing high-performance liquid chromatography (HPLC) was used to screen for novel gene variants and polymorphisms were genotyped in stored DNA from participants of the Leeds Family Study (537 subjects from 89 families). Genotype and haplotype analyses were carried out in STATA and PBAT, respectively. RESULTS: Twenty-five polymorphisms were identified; 11 in CEBPA, 12 in CEBPB and 2 in CEBPD. Several allelic variants were associated at a nominal 5% level with waist-to-hip ratio (-919G>A in CEBPA, -412G>T and 646C>T in CEBPB), leptin (1558G>A in CEBPA, -1051A>G and 1383T>- in CEBPB) and adiponectin (1382G>T and 1903G>T in CEBPB). Effects of CEBPA and CEBPB allelic variants were independent, but variants within each gene were in linkage disequilibrium. Several associations were observed between other obesity-related traits and allelic variants in CEBPA and CEBPB, but not CEBPD. CONCLUSION: These findings suggest that common allelic variants in CEBPA and CEBPB could influence abdominal obesity and related metabolic abnormalities associated with type 2 diabetes and cardiovascular disease in healthy White Northern European families, although results require independent confirmation.
Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína delta de Ligação ao Facilitador CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adiponectina/sangue , Cromatografia Líquida de Alta Pressão , Inglaterra/epidemiologia , Predisposição Genética para Doença , Haplótipos , Humanos , Leptina/sangue , Modelos Lineares , Desequilíbrio de Ligação , Obesidade/sangue , Obesidade/etnologia , Obesidade/fisiopatologia , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Medição de Risco , Fatores de Risco , Relação Cintura-Quadril , População Branca/genéticaRESUMO
OBJECTIVE: The relative balance between clot formation and fibrinolysis is considered to reflect thrombotic potential following vascular injury. The aims of the present study were to (1) to determine the contribution of genetic and environmental factors to variance in measures of clot structure/function in the Leeds Family Study, and (2) to determine the relationship between measures of clot structure/function and cardiovascular risk. METHODS AND RESULTS: Using high throughput turbidimetric assays, heritabilities of measures of clot formation, clot structure, and clot lysis were approximately 0.30. Fibrinogen contributed to variance in all measures and plasminogen activator inhibitor-1 to variance in lysis variables. Subjects at increased cardiovascular risk due to the presence of the metabolic syndrome (MetS) had increased clot density (MaxAbs(C): 0.358 [0.340, 0.375]au) and prolonged lysis times (Lys(T): 510 [6569, 7939]s) compared with those without MetS (MaxAbs(C): 0.319 [0.310, 0.328]au, P=0.003; Lys(T): 7221 [4884, 5328]s, P<0.001). Furthermore, measures of clot structure/function increased progressively with increasing number of MetS components. CONCLUSIONS: This study indicates that genetic factors contribute modestly to variance in clot structure/function and that clot structure/function is related to presence of the MetS and number of MetS components. Identification of the genetic and environmental factors influencing clot structure/function may further our understanding of the underlying factors predisposing to cardiovascular disease.
Assuntos
Coagulação Sanguínea/genética , Doenças Cardiovasculares/genética , Fibrinólise/genética , Variação Genética , Síndrome Metabólica/complicações , Trombose/genética , Adulto , Testes de Coagulação Sanguínea/métodos , Doenças Cardiovasculares/sangue , Europa (Continente) , Feminino , Fibrinogênio/metabolismo , Predisposição Genética para Doença , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Nefelometria e Turbidimetria , Linhagem , Inibidor 1 de Ativador de Plasminogênio/sangue , Fatores de Risco , Trombose/sangue , Trombose/complicações , Fatores de TempoRESUMO
The aim of this study was to determine whether complement C3 is an indicator of coronary artery disease (CAD). We measured plasma C3 and CRP levels in 278 patients undergoing coronary angiography for typical symptoms of CAD and 269 healthy age and sex matched controls. C3 levels were significantly higher in patients compared with controls (1.15 g/l and 0.92 g/l respectively; p<0.001). In the patient group, C3 levels correlated with BMI, fasting glucose, HbA1c, fibrinogen, CRP and HDL in both men and women. CRP levels were also higher in patients compared with controls (1.14 mg/l and 0.86 mg/l respectively; p=0.005) and correlated with markers of the metabolic syndrome. In a logistic regression model including C3, smoking, hypertension, cholesterol and diabetes, C3 was independently associated with CAD with an odds ratio of 3.20 for a 1 SD increase in C3 levels. In contrast, CRP was not independently associated with CAD in a similar regression analysis. In conclusion, both C3 and CRP plasma levels are elevated in patients with symptoms of CAD. However, C3 seems to be a better indicator of CAD than CRP in this study, suggesting that C3 could be an additional marker for risk stratification in atherosclerosis.
