Huntington's disease (HD) is caused by an expansion of a polyglutamine repeat of more than 35 units in the huntingtin protein. The expanded repeat length is inversely correlated with the age at onset (AAO); however, additional genetic factors apart from the expanded CAG repeat length can modify the course and the AAO in HD. Aberrations in macroautophagy have been observed in Huntington, Alzheimer, Parkinson, motor neuron and prion diseases. Therefore, we hypothesized that polymorphisms in autophagy-related (Atg) genes might contribute to the variation in the AAO. We initially tested eight single nucleotide polymorphisms in five Atg genes (Atg3, Atg5, Atg7, Atg16L1 and Beclin-1) for their frequency of ≥1%. Subsequently, we investigated the polymorphisms Atg7 V471A and Atg16L1 T281A for a disease-modifying effect in more than 900 European HD patients (including 2 populations consisting of 346 German patients and 327 patients of Italian descent). One polymorphism in the Atg7 gene that substitutes alanine for valine (V471A) showed a significant effect on the AAO (P=0.0050) and was associated with an earlier disease onset of 4 years. Our results further support the important pathophysiological role of autophagy in HD.

Background: Intrauterine growth restriction (IUGR) is known to affect the risk of adult diseases. consumption of lipogenic fructose is increasing, and it is used as an enhancer of metabolic syndrome in rat experiments. The effects of IUGR, postnatal fructose diet, and their interaction on the lipid profile and adiposity were studied in adult rats. Methods: IUGR was induced by providing pregnant rats with 50% of daily food intake. From 1 mo onward, half of the offspring received a fructose-rich diet and were then followed to the age of 1 and 6 mo, when plasma lipid, glucose, and insulin levels were measured. The adipose tissue was visualized by magnetic resonance imaging at the age of 6 mo. results: IUGR and fructose diet decreased body weight in adult rats. IUGR increased low-density lipoprotein cholesterol in 6-mo-old rats. The fructose diet evoked hypertriglyceridemia and hyperinsulinemia in both the sexes and decreased fasting glucose levels in female rats. Postnatal fructose diet increased lipid content percentage in the retroperitoneal and intra-abdominal adipose tissues in male rats. Interactions between IUGR and postnatal fructose diet were observed in adult weight in males. conclusion: These results demonstrate the importance of IUGR and fructose diet in adverse changes in lipid and glucose metabolism. t he terms "programming, " "fetal origins hypothesis, " and "metabolic imprinting" are used to describe the conditions in the uterus that can lead to possibly permanent or at least longterm changes in the systems involved in growth and metabolism (1,2). Epidemiological studies indicate that low birth weight is related to the risk of metabolic syndrome, type 2 diabetes, and atherosclerosis in adulthood. Poor fetal growth has also been linked to adult obesity, hypertension, and abnormal lipid metabolism (3).There is an interaction between the prenatal and postnatal environments on the health outcome of the offspring (3). Some, but not all, of the infants born small for gestational age show catch-up growth. Those experiencing early catch-up growth tend to have a higher BMI and fat mass as children (4), and according to some studies, they are at an increased risk for adult diseases as compared with those not showing catch-up growth (5). Therefore, it is interesting to elucidate the possible interactions between the prenatal growth and postnatal environment and their effects on the metabolic profile of the offspring.Fructose is a highly lipogenic sugar, and its consumption increases plasma triglyceride and low-density lipoprotein (LDL) cholesterol levels in humans (6). In rats, prolonged feeding of fructose induces moderate hypertension, glucose intolerance, insulin resistance, hyperinsulinemia, and hypertriglyceridemia, all of which are signs of metabolic syndrome (7,8). Therefore, fructose-fed rats are often used as a model of the metabolic syndrome (9).We performed a study of fetal growth restriction in rats. Initially, we aimed to determine if intrauterine growth restriction (IUGR) could affect plasma chole...

The variations in the LEPR gene are independently associated with early atherosclerosis and some of its risk factors. These variations could possibly affect leptin signaling and thereby modify the effects of leptin on the atherosclerotic process.