The mtDNA 15497 G/A polymorphism in cytochrome b in severe obese subjects from Southern Italy.

Background and aim: A large number of mitochondrial DNA (mtDNA) mutations have been implicated in degenerative diseases and aging. The aim of this study was to evaluate whether the 15497 G/A mtDNA polymorphism (G251S) in the cytochrome b subunit of respiratory complex III, which has been associated with obesity-related variables and lipid metabolism in a Japanese population, is associated with severe obesity also in adult Caucasians from southern Italy. Methods and results: Unrelated severely obese patients (n Z 317; BMI > 40 kg/m2) and controls (n Z 217; BMI < 25 kg/m2) from Southern Italy were genotyped by allelic discrimination TaqMan assay for the 15497 G/A mtDNA polymorphism. In obese patients fasting serum total cholesterol, triglycerides, HDL-cholesterol and glucose were measured enzymatically and sitting blood pressure and heart rate were also collected. Mean levels of total cholesterol, triglycerides and glucose were below the upper reference limit for healthy subjects. Female obese subjects showed lower levels of blood pressure and heart rate and higher levels of HDL cholesterol than male obese patients (P < 0.001). All the control subjects and 315/317 severely obese patients were homozygous for the G allele (wild type), whereas only 2/317, were females homozygous for the A allele. Conclusions: The mtDNA 15497 G/A polymorphism in cytochrome b was present in 0.6% obese subjects, two females whose lipid parameters and BMI were similar to those of the overall group. Therefore, this mutation may appear to contribute in rare instances to severe obesity but does not explain the majority of cases in our population. A more extensive genetic haplogroup characterization is required to identify associations to obesity in Caucasians

Bone mineral density in patients on home parenteral nutrition: a follow-up study.

Home artificial nutrition

Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes in severely obese adults living in southern Italy.

BACKGROUND: The genetic characterization of obese individuals could clarify the molecular mechanisms underlying body weight regulation and lead to targeted therapy. Here we report variants of the proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) genes detected in severely obese adults living in southern Italy. METHODS: A total of 196 unrelated nondiabetic severely obese individuals [111 females and 85 males; mean (SD) age, 32.2 (11.5) years; mean body mass index, 48.8 (8.1) kg/m(2)] and 100 normal-weight healthy volunteers (34 males and 66 females) entered the study. POMC and MC4R were genotyped by sequencing analysis. Leptin, insulin, glucose, and the lipid profile were measured in fasting serum samples. We used the protein truncation test to verify the stop-codon mutation. Anthropometric measurements, sitting blood pressure, and heart rate were also recorded. RESULTS: Of the obese participants, 1.5% had mutations in POMC exon 3 (new mutations, P231L and E244X; known, R236G) and 2.5% had MC4R mutations (new mutations, W174C, Q43X, S19fsX51, and I317V; known, A175T). These mutations were not present in the controls. Gene polymorphisms were identified in similar percentages of severely obese and nonobese individuals, i.e., respectively, 52.5% and 51% (POMC) and 1% and 2% (MC4R). CONCLUSIONS: We detected 2 new POMC mutations and 4 new MC4R mutations in a large number of severely obese adults living in southern Italy. These mutations, not present in normal-weight individuals, are further evidence that defects in the melanocortin pathway are related to severe obesity

Severe cardiomyopathy in a young patient with complete deficiency of adipose triglyceride lipase due to a novel mutation in PNPLA2 gene

We report the case of a 26 year-old male patient affected by neutral lipid storage myopathy with severe cardiac involvement. Patient parents were first cousins; a brother died at 3 years of age, during surgery. They referred that the child had always walked on toes, but he never presented weakness or difficulties in physical activity, compared to peers. The patient was first evaluated when he was 11 years-old and was reported to walk on toes, with difficulty to walk on heels, and to have mild calves hypertrophy and reduced tendon reflexes. Blood test revealed high values of CK (1657 U/L), while total and free carnitine levels were normal. Electromyography was normal; an effort test revealed excessive increase in lactic acid levels. He underwent a muscle biopsy that showed abnormal lipid storage. He was diagnosed to suffer from a lipid storage myopathy and therapy with riboflavin was started with some benefit to the patient. A neutral lipid storage myopathy was hypothesized and molecular analysis of the PNPLA2 gene revealed a homozygous novel deletion of seven nucleotides in exon 2 (c.41_47delGCTGCGG)