title: Effect of a polymorphism in the ND1 mitochondrial gene on human skeletal muscle mitochondrial function.
abstract: OBJECTIVE
  A non-silent polymorphism in the mitochondrial coding region of the ND1 gene, a subunit of reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase is associated with resting metabolic rate (RMR) in 245 non-diabetic Pima Indians. The purpose of this investigation was to determine the effect of the ND1 gene polymorphism on mitochondrial function in 14 male Pima Indians.
  
  
  METHODS
  Seven subjects with an A at site 3547 of the ND1 gene (Ile at amino acid 81), and seven with a G at this site (Val) were studied. Mitochondria were isolated from 0.8 to 1.5 g of skeletal muscle obtained by needle biopsy of the lateral quadriceps muscle. In intact mitochondria, maximal (state-3) and resting (state-4) respiration rates were measured polarographically at 37 degrees C with a variety of single substrates or substrate combinations. Disrupted mitochondria were analyzed for maximal capacities through the entire electron transport chain (ETC) (NADH oxidase (NADHOX)), as well as through a segment of Complex I that is independent of the ND1 component (NADH-ferricyanide (NADH-FeCN) reductase).
  
  
  RESULTS
  Mitochondria were well coupled and exhibited higher respiratory control ratios (RCRs) than rodent muscle. There were no differences between the two groups for any of the measured parameters.
  
  
  CONCLUSIONS
  These results indicate that the cause of the observed association between RMR and the ND1 polymorphism is not related to in vitro mitochondrial function.
authors.affiliation: Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado at Denver and Health Sciences Center, Denver, CO, USA. Matthew.Jackman@uchsc.edu
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Jackman
authors.forename: E
authors.initials: E
authors.lastname: Ravussin
authors.forename: M J
authors.initials: MJ
authors.lastname: Rowe
authors.forename: R
authors.initials: R
authors.lastname: Pratley
authors.forename: M R
authors.initials: MR
authors.lastname: Milner
authors.forename: W T
authors.initials: WT
authors.lastname: Willis
mesh_terms: D000328:Adult; D001481:Basal Metabolism / Q000235:genetics / Q000502:physiology; D001706:Biopsy; D015331:Cohort Studies; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D050259:Genes, Mitochondrial / Q000235:genetics*; D006801:Humans; D007198:Indians, North American; D008297:Male; D008931:Mitochondria, Muscle / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009245:NADH Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D045222:Electron Transport Chain Complex Proteins; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human