Parental diabetes status reveals association of mitochondrial DNA haplogroup J1 with type 2 diabetes.
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.
Feder
Jeanette
J
Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. federj@bgu.ac.il
Ovadia
Ofer
O
Blech
Ilana
I
Cohen
Josef
J
Wainstein
Julio
J
Harman-Boehm
Ilana
I
Glaser
Benjamin
B
Mishmar
Dan
D
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
D004272:DNA, Mitochondrial