title: Detailed analysis of variation at and around mitochondrial position 16189 in a large Finnish cohort reveals no significant associations with early growth or metabolic phenotypes at age 31 years.
abstract: BACKGROUND
  Mitochondrial dysfunction is increasingly implicated in pathogenesis of adult metabolic disease. Rare mitochondrial (mt) DNA mutations impair glucose homeostasis, but the contribution of common variants is unclear. In small studies, variation within the OriB origin of replication (at mt16189 in particular) has been associated with both early growth and adult metabolic phenotypes and may contribute to life-course relationships between the two.
  
  
  OBJECTIVE
  The aim was to study a large well-characterized cohort to determine whether previously reported small-scale associations between OriB sequence variation and early growth and adult metabolic phenotypes are robust.
  
  
  METHODS
  This was a genetic association study of 5470 individuals from the population-based Northern Finland Birth Cohort of 1966, followed prospectively from pregnancy to age 31 yr.
  
  
  METHODS
  We measured indices of early growth (including birth weight, placental weight, and ponderal index) and adult metabolic homeostasis (including body mass index, fasting glucose and insulin, indices of insulin action and secretion) and their relationship to variation in the OriB region.
  
  
  RESULTS
  Previously reported associations could not be confirmed. There were no significant (P < 0.01, uncorrected) associations between OriB sequence variation and measures of early growth including birth weight (P = 0.52, comparing individuals with mt16189T to those with a homopolymeric C-tract) and placental weight (P = 0.49). There were no significant associations with adult metabolic phenotypes including fasting glucose (P = 0.07), fasting insulin (P = 0.42), and homeostatic model assessment-derived measures of insulin sensitivity or secretion (P = 0.45 and P = 0.56, respectively).
  
  
  CONCLUSIONS
  Despite substantial power to detect previously reported effects, mtDNA variations around OriB are not major contributors to variation in early growth and metabolic phenotypes during early adulthood.
authors.affiliation: Women's Centre Level 3, University of Oxford, Oxford OX3 7LJ, United Kingdom.
authors.forename: Sreena
authors.initials: S
authors.lastname: Das
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Bennett
authors.forename: Ulla
authors.initials: U
authors.lastname: Sovio
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.forename: Hannu
authors.initials: H
authors.lastname: Martikainen
authors.forename: Anneli
authors.initials: A
authors.lastname: Pouta
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Stephen
authors.initials: S
authors.lastname: Franks
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
authors.forename: Joanna
authors.initials: J
authors.lastname: Poulton
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D015331:Cohort Studies; D004261:DNA Replication / Q000235:genetics / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D014644:Genetic Variation; D006128:Growth / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008660:Metabolism / Q000235:genetics* / Q000502:physiology; D009154:Mutation / Q000502:physiology*; D010641:Phenotype; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049629:Waist-Hip Ratio
chemical_list: D001786:Blood Glucose; D004272:DNA, Mitochondrial; D008055:Lipids