title: Parental diabetes status reveals association of mitochondrial DNA haplogroup J1 with type 2 diabetes.
abstract: BACKGROUND
  Although mitochondrial dysfunction is consistently manifested in patients with Type 2 Diabetes mellitus (T2DM), the association of mitochondrial DNA (mtDNA) sequence variants with T2DM varies among populations. These differences might stem from differing environmental influences among populations. However, other potentially important considerations emanate from the very nature of mitochondrial genetics, namely the notable high degree of partitioning in the distribution of human mtDNA variants among populations, as well as the interaction of mtDNA and nuclear DNA-encoded factors working in concert to govern mitochondrial function. We hypothesized that association of mtDNA genetic variants with T2DM could be revealed while controlling for the effect of additional inherited factors, reflected in family history information.
  
  
  METHODS
  To test this hypothesis we set out to investigate whether mtDNA genetic variants will be differentially associated with T2DM depending on the diabetes status of the parents. To this end, association of mtDNA genetic backgrounds (haplogroups) with T2DM was assessed in 1055 Jewish patients with and without T2DM parents ('DP' and 'HP', respectively).
  
  
  RESULTS
  Haplogroup J1 was found to be 2.4 fold under-represented in the 'HP' patients (p = 0.0035). These results are consistent with a previous observation made in Finnish T2DM patients. Moreover, assessing the haplogroup distribution in 'DP' versus 'HP' patients having diabetic siblings revealed that haplogroup J1 was virtually absent in the 'HP' group.
  
  
  CONCLUSIONS
  These results imply the involvement of inherited factors, which modulate the susceptibility of haplogroup J1 to T2DM.
authors.affiliation: Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. federj@bgu.ac.il
authors.forename: Jeanette
authors.initials: J
authors.lastname: Feder
authors.forename: Ofer
authors.initials: O
authors.lastname: Ovadia
authors.forename: Ilana
authors.initials: I
authors.lastname: Blech
authors.forename: Josef
authors.initials: J
authors.lastname: Cohen
authors.forename: Julio
authors.initials: J
authors.lastname: Wainstein
authors.forename: Ilana
authors.initials: I
authors.lastname: Harman-Boehm
authors.forename: Benjamin
authors.initials: B
authors.lastname: Glaser
authors.forename: Dan
authors.initials: D
authors.lastname: Mishmar
mesh_terms: D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007585:Jews / Q000235:genetics; D016014:Linear Models; D010290:Parents
chemical_list: D004272:DNA, Mitochondrial