LDLR gene's promoter region hypermethylation in patients with familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein cholesterol (LDL-C) levels and a high risk of early coronary heart disease. Structural alterations in the LDLR, APOB, and PCSK9 genes were not found in 20-40% of patients diagnosed using the Dutch Lipid Clinic Network (DCLN) criteria. We hypothesized that methylation in canonical genes could explain the origin of the phenotype in these patients. This study included 62 DNA samples from patients with a clinical diagnosis of FH according to the DCLN criteria, who previously tested negative for structural alterations in the canonical genes, and 47 DNA samples from patients with normal blood lipids (control group). All DNA samples were tested for methylation in the CpG islands of the three genes. The prevalence of FH relative to each gene was determined in both groups and the respective prevalence ratios (PRs) were calculated. The methylation analysis of APOB and PCSK9 was negative in both groups, showing no relationship between methylation in these genes and the FH phenotype. As the LDLR gene has two CpG islands, we analyzed each island separately. The analysis of LDLR-island1 showed PR = 0.982 (CI 0.33-2.95; χ2 = 0.001; p = 0.973), also suggesting no relationship between methylation and the FH phenotype. Analysis of LDLR-island2 showed a PR of 4.12 (CI 1.43-11.88; χ2 = 13,921; p = 0.00019), indicating a possible association between methylation on this island and the FH phenotype.

What is the best equation to estimate the basal energy expenditure of climacteric women?

OBJECTIVES: The methods currently available for the measurement of energy expenditure in patients, such as indirect calorimetry and double-labelled water, are expensive and are limited in Brazil to research projects. Thus, equations for the prediction of resting metabolic rate appear to be a viable alternative for clinical practice. However, there are no specific equations for the Brazilian population and few studies have been conducted on Brazilian women in the climacteric period using existing and commonly applied equations. On this basis, the objective of the present study was to investigate the concordance between the predictive equations most frequently used and indirect calorimetry for the measurement of resting metabolic rate. METHODS: We calculated the St. Laurent concordance correlation coefficient between the equations and resting metabolic rate calculated by indirect calorimetry in 46 climacteric women. RESULTS: The equation showing the best concordance was that of the FAO/WHO/UNU formula (0.63), which proved to be better than the Harris & Benedict equation (0.55) for the sample studied. CONCLUSIONS: On the basis of the results of the present study, we conclude that the FAO/WHO/UNU formula can be used to predict better the resting metabolic rate of climacteric women. Further studies using more homogeneous and larger samples are needed to permit the use of the FAO/WHO/UNU formula for this population group with greater accuracy.

Climacteric, physically active women ingesting their routine diet oxidize more carbohydrates than lipids.

OBJECTIVE: To investigate the influence of a routine Brazilian diet on the rate of oxidation of energy substrates in climacteric, obese women, who came to the outpatient clinic of the Hospital of the School of Medicine of Ribeirao Preto (HCFMRP-USP). METHODS: Subjects were recruited from outpatients at the Climacteric Clinic of the HCFMRP-USP, who were aged between 39 and 65 years and who voluntarily agreed to participate in this study. They were submitted to anthropometric measurements and indirect calorimetry for resting energy expenditure and substrate oxidation rate determination. RESULTS: The carbohydrate oxidation in the group of climacteric, obese women showed a significant positive correlation between energy consumption at rest and ingestion of carbohydrates (in grams); the subjects' rate of lipid intake showed a significant negative correlation with their body mass index, waist circumference, and daily total caloric intake. CONCLUSION: Carbohydrate intake and carbohydrate oxidation rate may contribute to weight gain in climacteric women.

Effect of hypocaloric meals with different macronutrient compositions on energy metabolism and lung function in obese women.

OBJECTIVE: We investigated the effect of hypocaloric mixed diets with different proportions of carbohydrate, protein, and fat on resting metabolic rate and the thermic effect of food in obese women. METHODS: Three mixed hypocaloric diets were consumed in random order during separate periods lasting 7 d each. Between each dietary period there was a washout period of 10 d. Diet 1 had a higher proportion of energy from carbohydrate (72%), diet 2 had a higher proportion of energy from protein (43%), and diet 3 had a higher proportion of energy from fat (68%). Indirect calorimetry and lung function tests were done after the completion of each 7-d diet. Seven obese women, ages 22 to 45 y and with body mass indexes of 32 to 59 kg/m(2), participated in the study. Oxygen consumption, carbon dioxide production, resting metabolic rate, and the thermic effect of food by indirect calorimetry were measured. Lung function tests included spirometry in the seated and upright positions, arterial blood gas analysis, and maximal inspiratory and expiratory pressures. RESULTS: There were no statistically significant differences in the resting metabolic rate and the thermic effect of food resulting from the three diets. The mean resting metabolic rates (kJ/d) were 7453 +/- 1446 for diet 1, 7461 +/- 1965 for diet 2, and 7076 +/- 2048 for diet 3. The mean thermic effects of food (kcal/min) were -0.02 +/- 0.07 for diet 1, -0.01 +/- 0.25 for diet 2, and 0.05 +/- 0.13 for diet 3. Lung function tests were normal before and after the hypocaloic diets: partial pressure of oxygen (mmHg) values were 81 +/- 13, 77 +/- 8, and 78 +/- 11 for diets 1 to 3, respectively; and partial pressure of carbon dioxide (mmHg) were 37 +/- 4, 37 +/- 3, and 37 +/- 4 for diets 1 to 3, respectively. CONCLUSIONS: Obese women with normal lung function tests and consuming mixed hypocaloric diets showed no alteration in resting metabolic rate and a reduced or absent thermic effect of food independently of the macronutrient composition.