group to cytosine residues in the dinucleotide sequence CpG. 1 A lack of alimentary methyl-group donors, like folate, owing to starvation, may be the underlying cause of both elevated homocysteine and DNA hypomethylation in AN.To further investigate possible epigenetic contributions to the pathophysiology of eating disorders, we analyzed the expression and promoter-specific DNA methylation of two genes, SNCA and HERP, recently described to be altered in alcohol dependence. 5,7 We found a decreased SNCA expression in patients with AN, which was associated with a DNA hypermethylation of the SNCA promoter. Although showing a decreased expression of SNCA, we failed to find hypermethylation in the BN groups possibly owing to a lack of power of the study, as there was a trend towards hypermethylation when compared to controls (t-test; P = 0.083), but this was lost after correction for multiple comparisons. The observation that unchanged promotermethylation of the HERP gene was associated with a gene expression comparable to that in the control group may suggest that normal patterns of DNA methylation can be kept constant in the promoter regions of certain genes despite a potential lack of methyl groups.In conclusion, we found alterations of epigenetic DNA methylation in females with AN. These findings need to be replicated in a larger sample and different genes should be analyzed, and different methods of analyzing methylation patterns of the DNA should be applied. The restriction enzyme-based approach that we have chosen has some disadvantages when compared to bisulfite sequencing methods, mainly the limitation of analysis to one CpG element in the promoter and the need for reliable digestion results. Longitudinal observations, comparing acute illness with the situation after refeeding and recovery, are warranted. Profound knowledge of the epigenetics of eating disorders may help in understanding the geneenvironment nexus postulated for the disorder.

Our results indicate that genetic variants in/near these genes contribute to obesity susceptibility in childhood and highlight the age at which they begin to affect obesity-related phenotypes.

Sex steroid hormones have multiple effects on lipid metabolism. We investigated the association between two common single nucleotide polymorphisms of the estrogen receptor 2 gene (ESR2), 1082G4A and 1730A4G, and PROGINS polymorphism of the progesterone receptor gene (PGR) with lipoprotein levels in a cross-sectional study with 472 women of European descent. The women were classified into three subgroups according to hormonal status, premenopausal women (n ¼ 187; mean age ¼ 3479.7 years), postmenopausal women exposed to hormone replacement therapy (HRT) (n ¼ 118; 5676.7 years) and postmenopausal women unexposed to HRT (n ¼ 167; 5879.8 years). The premenopausal and postmenopausal women exposed to HRT, both carriers of G/A genotype, exhibited LDL-C (P ¼ 0.027 and 0.001, respectively) and T-chol levels (P ¼ 0.035 and 0.001, respectively) lower than carriers of G/G genotype. This association was not observed in postmenopausal women unexposed to HRT. These results suggest that ESR2 1082G4A genotype may influence LDL-C levels in women with abundant estrogen levels, due to either endogenous or exogenous sources. INTRODUCTIONEndogenous and exogenous sex steroid hormones have multiple effects on lipid and lipoprotein metabolism. The oral estrogen replacement therapy (ERT) in postmenopausal women decreases serum total cholesterol (T-chol) and lowdensity lipoprotein cholesterol (LDL-C) concentrations, as well as increases serum high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels. 1 The effects of combined (estrogen plus progestin) hormone replacement therapy (HRT) are uncertain; the addition of a progestogen to estrogens tends to attenuate the increase in serum HDL-C and the decrease in LDL-C, obtained with ERT, although this effect seems to be related to the dose and to androgenic potency of the progestogen. 2 The beneficial changes in these lipoproteins should be associated with at least 30-35% decline in coronary heart disease (CHD) incidence. 3 However, the results from the Heart and Estrogen/Progestin Replacement Study (HERS) 4 and the Women's Health Initiative (WHI) trial 5 demonstrated that oral HRT does not provide cardiovascular benefit or even some evidence of cardiovascular harm.

BackgroundOur goal was to analyze the association of the fat mass and obesity- associated (FTO) gene rs9939609 variant (T/A) with the anthropometric and dietary intake phenotypes related to obesity in Brazilian children.MethodsWe analyzed the association of this single nucleotide polymorphism (SNP) with phenotypes related to the accumulation of body mass in a cohort of 348 children followed from the time of birth until 8 years old and then replicated the main findings in an independent schoolchildren sample (n = 615).ResultsAt the age of 4, we observed a significant association between the A/A genotype and a higher mean BMI Z-score (P = 0.036). At the age of 8, the A/A individuals still presented with a higher BMI Z-score (P = 0.011) and with marginal differences in the volume of subcutaneous fat (P = 0.048). We replicated these findings in the schoolchildren sample, which showed that those with at least one copy of the A allele presented with a higher BMI Z-score (P = 0.029) and volume of subcutaneous fat (P = 0.016).ConclusionOur results indicate that this FTO variant is associated with increased body mass and subcutaneous fat in Brazilian children beginning at the age of 4.

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