Assuntos
Tireotropina , Tri-Iodotironina , Anticorpos , Humanos , Iodeto Peroxidase , Peroxidase , Tireoglobulina , Hormônios Tireóideos , TiroxinaRESUMO
In this study we investigated an asymptomatic 55-year-old Lebanese woman with factor XI deficiency. The F11 gene was analyzed and a cross reacting material positive (CRM+) variant, Thr575Met, was identified in homozygosity in the proband, and in heterozygosity in four of her siblings.
Assuntos
Deficiência do Fator XI/genética , Mutação de Sentido Incorreto , Domínio Catalítico , Fator XI/genética , Saúde da Família , Feminino , Homozigoto , Humanos , Líbano , Pessoa de Meia-Idade , LinhagemRESUMO
BACKGROUND: The effect of statins on insulin resistance is controversial and poorly studied in nondiabetic subjects. In addition, the effect of statins on leptin and adiponectin has never been studied. METHODS: Forty healthy nondiabetic volunteers (22 men and 18 women) aged 28 to 72 were randomized either to placebo or pravastatin 40 mg daily for a 12-week period. Insulin resistance, assessed using the Quantitative Insulin Sensitivity Check Index (QUICKI), as well as serum leptin and adiponectin levels, was measured at baseline and at the end of therapy. RESULTS: Pravastatin treatment decreased total cholesterol, low-density lipoprotein cholesterol, and triglycerides levels by 24%, 32%, and 14%, respectively ( P < .05 for all), but did not affect glucose and insulin levels, the (QUICKI) index, and adiponectin and leptin levels. When stratification was performed according to QUICKI index or sex, no significant differences were observed in the prevalues and postvalues of leptin, adiponectin, or QUICKI index in the pravastatin group. Adiponectin, leptin, and QUICKI index were statistically higher in women than in men ( P < .001 for both variables). Adiponectin was negatively correlated with body mass index (BMI; r = -0.39, P < .05) and positively correlated with the QUICKI index ( r = 0.54, P < .001) and with high-density lipoprotein cholesterol ( r = 0.50, P < .01). The relation between adiponectin and QUICKI index remained significant after adjustment for sex and BMI ( P = .005 and P = .007, respectively). Leptin was only related to BMI ( r = 0.57, P < .001) and to sex ( P < .001) with no significant correlations with lipid parameters or QUICKI index. Both sex and BMI are independent predictors of leptin ( P < .001 and P < .001). CONCLUSION: A 12-week treatment with pravastatin 40 mg/d does not change the QUICKI index and leptin and adiponectin levels in healthy volunteers. In addition, our results emphasize the importance of sex and BMI in the determination of both adiponectin and leptin. Adiponectin was also related to QUICKI index, whereas this relation was not found with leptin.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Leptina/sangue , Pravastatina/farmacologia , Adiponectina , Adulto , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Valores de ReferênciaRESUMO
In this study, a Lebanese woman with severe factor XI deficiency as well as several unaffected family members were analysed. The F11 gene was screened by polymerase chain reaction amplification of all 15 exons, including intron-exon junctions followed by single-strand conformational analysis. Variant single-strand conformational analysis profiles were obtained for exon 13; sequencing of these products allowed the identification of a novel missense mutation (Trp501Cys) situated in the catalytic domain, in homozygosity in the proband.
Assuntos
Deficiência do Fator XI/genética , Mutação de Sentido Incorreto , Adulto , Domínio Catalítico , Análise Mutacional de DNA/métodos , Éxons , Saúde da Família , Feminino , Homozigoto , Humanos , LíbanoRESUMO
OBJECTIVE: We analyzed the relation of osteoprotegerin (OPG) with insulin sensitivity, lipid profile, serum glutamic pyruvic transaminase (SGPT), adipocytokines, and C-reactive protein (CRP) in obese and non-obese subjects. METHODS: In the study, 170 subjects (106 obese and 64 non-obese, sex ratio female/male=2.03) were included. Thirty-two obese subjects were reevaluated 6 months after the weight loss induced by bariatric surgery. RESULTS: OPG did not differ between obese and non-obese subjects (respective mean values 5.17 and 4.96 pmol/l) or according to gender, but was positively correlated with age (P<0.0001 for both groups). OPG was statistically higher in 18 obese diabetic subjects compared with non-diabetics (P=0.03). After adjustment for age, no significant correlation was found between OPG and body mass index (BMI), waist, systolic and diastolic blood pressure, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, leptin, and adiponectin in both the obese and non-obese subjects. However, OPG was positively correlated with homeostasis model assessment (HOMA) index and SGPT levels in obese subjects at baseline (r=0.295, r=0.20, P<0.05) and after adjustment for age (r=0.28, r=0.20, P<0.05). OPG was also significantly correlated with CRP; this correlation persisted after adjustment for age in obese subjects (r=0.30, P<0.01). In a multivariate analysis in the obese group, HOMA index and CRP were independent predictors of OPG while SGPT was not. Six months post-surgery, OPG did not change, despite a significant reduction in glucose, SGPT, cholesterol, triglycerides, CRP, and leptin values (P=0.02, P=0.006, P=0.007, P<0.001, P<0.001, P<0.001 respectively) and a significant increase in adiponectin and HDL values (P<0.001 for both variables). CONCLUSION: Our results show that in obese subjects, OPG is not related to BMI. However, we describe new relationships between OPG and both HOMA index and CRP.
Assuntos
Adipocinas/sangue , Peso Corporal/fisiologia , Proteína C-Reativa/metabolismo , Resistência à Insulina , Obesidade/metabolismo , Osteoprotegerina/sangue , Adulto , Alanina Transaminase/sangue , Cirurgia Bariátrica , Doenças Cardiovasculares/epidemiologia , HDL-Colesterol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Homeostase/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/cirurgia , Análise de Regressão , Fatores de Risco , Triglicerídeos/sangue , Redução de Peso/fisiologiaRESUMO
Congenital afibrinogenemia, the most severe form of fibrinogen deficiency, is characterized by the complete absence of fibrinogen. The disease is caused by mutations in 1 of the 3 fibrinogen genes FGG, FGA, and FGB, clustered on the long arm of human chromosome 4. The majority of cases are due to null mutations in the FGA gene although one would expect the 3 genes to be equally implicated. However, most patients studied so far are white, and therefore the identification of causative mutations in non-European families is necessary to establish if this finding holds true in all ethnic groups. In this study, we report the identification of a novel nonsense mutation (Arg134Xaa) in the FGG gene responsible for congenital afibrinogenemia in 10 patients from Lebanon. Expression studies in COS-7 cells demonstrated that the Arg134Xaa codon, which is encoded by adjacent exons (TG-intron 4-A) affected neither mRNA splicing nor stability, but led to the production of an unstable, severely truncated fibrinogen gamma chain that is not incorporated into a functional fibrinogen hexamer.