title: Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes in severely obese adults living in southern Italy.
abstract: 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.
authors.affiliation: Facoltà di Scienze Motorie, Università degli Studi Parthenope di Napoli, Naples, Italy.
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Buono
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pasanisi
authors.forename: Carmela
authors.initials: C
authors.lastname: Nardelli
authors.forename: Luigi
authors.initials: L
authors.lastname: Ieno
authors.forename: Silvana
authors.initials: S
authors.lastname: Capone
authors.forename: Rosario
authors.initials: R
authors.lastname: Liguori
authors.forename: Carmine
authors.initials: C
authors.lastname: Finelli
authors.forename: Giovannangelo
authors.initials: G
authors.lastname: Oriani
authors.forename: Franco
authors.initials: F
authors.lastname: Contaldo
authors.forename: Lucia
authors.initials: L
authors.lastname: Sacchetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D044105:Receptor, Melanocortin, Type 4; D011333:Pro-Opiomelanocortin