Aidil Fonseca

The role of HFE mutations on iron metabolism in beta-thalassemia carriers

AbstractHereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and progressive storage resulting in organ damage. HFE gene mutations C282Y and H63D are responsible for the majority of HH cases. A third HFE mutation, S65C, has been associated with the development of a mild form of hemochromatosis. The beta-thalassemia trait is characterized by mild, ineffective erythropoiesis that can induce excess iron absorption and ultimately lead to iron overload. The aim of this study was to evaluate the effect of genetic markers (HFE mutations C282Y, H63D, and S65C) on the iron status of beta-thalassemia carriers. A total of 101 individuals heterozygous for beta-thalassemia and 101 normal control individuals were studied. The allelic frequencies of C282Y (1.5 versus 3.5%), H63D (15.3 versus 18.3%), and S65C (1.0 versus 1.5%) did not differ significantly between beta-thalassemia carriers and normal controls. Serum iron (P=0.029) and transferrin saturation (P=0.009) were increased in beta-thalassemia carriers heterozygous for H63D mutation. The number of subjects carrying C282Y or S65C mutations was too low to conclude their effect on the iron status. These results suggest that the beta-thalassemia trait tends to be aggravated with the coinheritance of H63D mutation, even when present in heterozygosity.

APOE genotypes and dyslipidemias in a sample of the Portuguese population.

Abstract The objective of this work was to study the distribution of apolipoprotein E ( APOE) genotypes in a sample of the Portuguese population, and its association with the dyslipidemias observed. Study participants were healthy users of local Public Health Laboratories in six regions of mainland Portugal (Porto, Vila Real, Viseu, Lisboa, Portalegre and Faro). A total of 779 men and 1153 women aged 15–74years agreed to participate. Fasting lipid levels and APOE genotypes were determined centrally at the National Institute of Health in Lisboa. The frequency distribution of APOE alleles was: ε2=5.3%, ε3=84.9% and ε4=9.8%. Dyslipidemias were present in 66.6% of men and 60.7% of women. Comparison of APOE genotypes and relative allele frequencies showed that in dyslipidemic compared to normolipidemic subjects, the ε4 allele was more frequent in both sexes, although in a more pronounced way in men than in women due to higher frequencies of ε3/ ε4 and ε4/ ε4 genotypes. The known association of the ε4 allele with high cholesterol levels, the association of the ε2 allele with low cholesterol levels, and the association of the ε2 allele with high levels of triglycerides and low levels of high-density lipoprotein-cholesterol were confirmed in this study.

Relação entre a leptina, a massa corporal e a síndrome metabólica numa amostra da população adulta

OBJECTIVE To analyze the relationship between leptin and obesity expressed as body mass index (BMI) and certain components of the metabolic syndrome (MS) in an adult population. METHODS The study included 103 subjects, 42 men and 61 women, aged over 30 years, clinically defined as non-diabetic but with personal or family history of cardiovascular disease. All subjects underwent fasting blood measurements of leptin, insulin, glucose, glucose after ingestion of 75g glucose, HDL cholesterol and triglycerides, and insulin resistance (IR) and BMI were calculated. RESULTS BMI as an index of overall adiposity was strongly associated with serum leptin. BMI rose as serum leptin levels increased from the first to the third tertile; the correlation between leptin and BMI was strong, r=0.524 in men and r=0.603 in women, with high statistical significance (p<0.001); BMI was the best predictor of hyperleptinemia on ROC analysis, with area under the curve (AUC)=0.81 in men and 0.84 in women. The association between leptin and obesity (BMI ≥30kg/m(2)) showed high odds ratios (OR) in both sexes (10.11 in men, 6.00 in women) on univariate regression analysis and 9.30 in men and 8.21 in women on multivariate regression analysis. Hyperinsulinemia and IR strongly influenced hyperleptinemia. Leptin was the best predictor of IR in both sexes (AUC=0.89 in men and 0.85 in women), and IR in men (AUC=0.79) and hyperinsulinemia in women (AUC=0.78) were the best predictors of hyperleptinemia after BMI. The correlations between leptin and IR, and leptin and insulinemia, were strong in both sexes. With regard to MS components, increased serum levels of the study variables were observed as leptin concentrations rose from the first to the third tertile (with the exception of HDL cholesterol, which decreased). CONCLUSION Elevated serum leptin, particularly in obese individuals, should be taken as a warning sign of energy imbalance, poor diet, hyperinsulinemia, insulin resistance, or changes in other metabolic risk factors that are strongly associated with cardiovascular disease and type 2 diabetes.

Reply to the Letter to the Editor “Are leptin levels a cause or an indicator of cardiovascular risk?”

Some time ago the Journal published an article by us entitled ‘‘Relationship between leptin and body mass and metabolic syndrome in an adult population’’ (Rev Port Cardiol 2012;31 11:711-719), which was the subject of a Letter to the Editor from investigators in Turkey. We are pleased to note that some of the comments in this letter were in support of our article, which we appreciate, while others are somewhat critical. These criticisms appear to apply to the title of our article, since we correlated body mass index (BMI) with leptin levels without taking into consideration the effect of smoking as a cardiovascular risk factor, which can affect serum leptin levels. We used BMI as a means of quantifying obesity, which we proceeded to relate to the risk factors under analysis. With regard to the title of the Letter to the Editor, we would like to make the following points. Obesity, in particular changes in adipose tissue, has harmful effects in organs including the pancreas, liver, muscle and especially the heart. Insulin resistance (IR) is the main mechanism behind these effects, resulting in other disorders including dyslipidemia, hyperinsulinemia and impaired glucose tolerance (as we observed in our study population and attempted to explain), leading inexorably to atherosclerosis (and hence cardiovascular disease) and type 2 diabetes. As stated in the Results and Discussion sections of our article, higher serum leptin levels are associated with significantly increased IR and serum insulin (and in fact with all the