title: The 16189 variant of mitochondrial DNA occurs more frequently in C282Y homozygotes with haemochromatosis than those without iron loading.
abstract: BACKGROUND
  Patients with hereditary haemochromatosis (HH) are usually homozygous for the C282Y mutation in the HFE gene. They have variable expression of iron overload and present with a variety of complications, including liver disease, diabetes, arthropathy, fatigue, and cardiomyopathy. The mitochondrial 16189 variant is associated with diabetes, dilated cardiomyopathy, and low body fat at birth, and might contribute to genetic predisposition in further multifactorial disorders. The objective of this study was to determine the frequency of the 16189 variant in a range of patients with haemochromatosis, who had mutations in the HFE gene.
  
  
  METHODS
  Blood DNA was analysed for the presence of the 16189 variant in British, French, and Australian C282Y homozygotes and controls, with known iron status, and in birth cohorts.
  
  
  RESULTS
  The frequency of the mitochondrial 16189 variant was found to be elevated in individuals with haemochromatosis who were homozygous for the C282Y allele, compared with population controls and with C282Y homozygotes who were asymptomatic (42/292 (14.4%); 102/1186 (8.6%) (p = 0.003); and 2/64 (3.1%) (p = 0.023), respectively).
  
  
  CONCLUSIONS
  Iron loading in C282Y homozygotes with HH was exacerbated by the presence of the mitochondrial 16189 variant.
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Livesey
authors.forename: V L C
authors.initials: VL
authors.lastname: Wimhurst
authors.forename: K
authors.initials: K
authors.lastname: Carter
authors.forename: M
authors.initials: M
authors.lastname: Worwood
authors.forename: E
authors.initials: E
authors.lastname: Cadet
authors.forename: J
authors.initials: J
authors.lastname: Rochette
authors.forename: A G
authors.initials: AG
authors.lastname: Roberts
authors.forename: J J
authors.initials: JJ
authors.lastname: Pointon
authors.forename: A T
authors.initials: AT
authors.lastname: Merryweather-Clarke
authors.forename: M L
authors.initials: ML
authors.lastname: Bassett
authors.forename: A-M
authors.initials: AM
authors.lastname: Jouanolle
authors.forename: A
authors.initials: A
authors.lastname: Mosser
authors.forename: V
authors.initials: V
authors.lastname: David
authors.forename: J
authors.initials: J
authors.lastname: Poulton
authors.forename: K J H
authors.initials: KJ
authors.lastname: Robson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics*; D015331:Cohort Studies; D003545:Cysteine / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000473:pathology; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D014443:Tyrosine / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014443:Tyrosine; D003545:Cysteine