Because epigenetic changes may cause or contribute to gene silencing, our data may have relevance for the therapeutic approach to FRDA. Since the analysis can be performed in peripheral blood leucocytes (PBL), evaluation of the methylation status of specific CpG sites in FRDA patients could be a convenient biomarker.

Friedreich's ataxia is an autosomal recessive neurodegenerative disease that is due to the loss of function of the frataxin protein. The molecular basis of this disease is still a matter of debate and treatments have so far focused on managing symptoms. Drugs that can increase the amount of frataxin protein offer a possible therapy for the disease. One such drug is recombinant human erythropoietin (rhu-EPO). Here, we report the effects of rhu-EPO on frataxin mRNA and protein in primary fibroblast cell cultures derived from Friedreich's ataxia patients. We observed a slight but significant increase in the amount of frataxin protein. Interestingly, we did not observe any increase in the messenger RNA expression at any of the times and doses tested, suggesting that the regulatory effects of rhu-EPO on the frataxin protein was at the post-translational level. These findings could help the evaluation of the treatment with erythropoietin as a potential therapeutic agent for Friedreich's ataxia.

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Background: It is widely accepted that Type 2 Diabetes Mellitus (T2DM) and other complex diseases are the product of complex interplay between genetic susceptibility and environmental causes. To cope with such a complexity, all the statistical and conceptual strategies available should be used. The working hypothesis of this study was that two wellknown T2DM risk factors could have diverse effect in individuals carrying different genotypes. In particular, our effort was to investigate if a well-defined group of genes, involved in peripheral energy expenditure, could modify the impact of two environmental factors like age and obesity on the risk to develop diabetes. To achieve this aim we exploited a multianalytical approach also using dimensionality reduction strategy and conservative significance correction strategies.

OBJECTIVE -We explore the relationship among BMI, habitual diet, and the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor (PPAR)␥2.RESEARCH DESIGN AND METHODS -The Pro12Ala variant was characterized in 343 unrelated type 2 diabetic patients who were consecutively seen at the outpatient clinic of a health district of the province of Naples. Anthropometric and laboratory parameters were measured; habitual diet was assessed by a validated semiquantitative food frequency questionnaire.RESULTS -The overall frequency of Ala12 was 12% (n ϭ 42). BMI was significantly higher in Ala carriers than non-Ala carriers, whereas total daily energy intake or macronutrient composition of the diet were similar in the two groups. For further analysis, participants were stratified according to genotype and sex-specific quartiles of energy intake. BMI increased in both genotype groups with increasing energy intake (P Ͻ 0.03). BMI was similar in Ala carriers and non-Ala carriers (30.0 vs. 30.1 kg/m 2 , P Ͼ 0.10) in the lower quartile of energy intake but significantly higher in Ala carriers in the upper quartile (36.0 vs. 32.1 kg/m 2 , P Ͻ 0.001). Average daily energy intake and diet composition were comparable within each quartile for carriers or noncarriers of the Ala allele. Relative to the noncarriers, Ala carriers had a significantly lower energy intake per kilogram body weight, thus suggesting that the Ala allele is associated with a higher food efficiency. The confounding role of medications, glucose control, and physical exercise was ruled out.CONCLUSIONS -This study provides evidence of a differential susceptibility to fat accumulation, and, hence, weight gain, in response to habitual high energy intake for Ala carriers compared with Pro/Pro homozygotes. Diabetes Care 30:1156 -1161, 2007O ver the last two decades, the prevalence of overweight and obesity has increased worldwide (1). Although the epidemic of obesity is largely caused by dietary and other lifestyle-related factors, the genetic background likely plays a role in determining the differences among individuals in gaining weight under the same environmental conditions. Studies on rodents have shown a different susceptibility to obesity induced by a high-fat diet (2). Likewise, the understanding of the etiology of complex traits, such as obesity in humans, requires the exploration of the combined gene-environment effect (3,4).Among the genetic factors potentially involved in the etiology of obesity, the gene encoding for the peroxisome proliferator-activated receptor (PPAR)␥, a nuclear receptor that regulates adipocyte differentiation, lipid storage, fat-specific gene expression, and insulin action, has attracted much attention.Of the three PPAR␥ isoforms, PPAR␥2 mRNA is the most abundantly and specifically expressed in adipose tissue, which makes PPAR␥2 a candidate gene for the regulation of body weight. Furthermore, PPAR␥2 can bind a variety of compounds including fatty acids of dietary origin, and it is, therefore, an interesting gene for gene...