Mitochondrial DNA haplogroup T is associated with coronary artery disease and diabetic retinopathy: a case control study.
BACKGROUND
There is strong and consistent evidence that oxidative stress is crucially involved in the development of atherosclerotic vascular disease. Overproduction of reactive oxygen species (ROS) in mitochondria is an unifying mechanism that underlies micro- and macrovascular atherosclerotic disease. Given the central role of mitochondria in energy and ROS production, mitochondrial DNA (mtDNA) is an obvious candidate for genetic susceptibility studies on atherosclerotic processes. We therefore examined the association between mtDNA haplogroups and coronary artery disease (CAD) as well as diabetic retinopathy.


METHODS
This study of Middle European Caucasians included patients with angiographically documented CAD (n = 487), subjects with type 2 diabetes mellitus with (n = 149) or without (n = 78) diabetic retinopathy and control subjects without clinical manifestations of atherosclerotic disease (n = 1527). MtDNA haplotyping was performed using multiplex PCR and subsequent multiplex primer extension analysis for determination of the major European haplogroups. Haplogroup frequencies of patients were compared to those of control subjects without clinical manifestations of atherosclerotic disease.


RESULTS
Haplogroup T was significantly more prevalent among patients with CAD than among control subjects (14.8% vs 8.3%; p = 0.002). In patients with type 2 diabetes, the presence of diabetic retinopathy was also significantly associated with a higher prevalence of haplogroup T (12.1% vs 5.1%; p = 0.046).


CONCLUSIONS
Our data indicate that the mtDNA haplogroup T is associated with CAD and diabetic retinopathy in Middle European Caucasian populations.
Kofler
Barbara
B
Department of Pediatrics, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria. b.kofler@salk.at
Mueller
Edith E
EE
Eder
Waltraud
W
Stanger
Olaf
O
Maier
Richard
R
Weger
Martin
M
Haas
Anton
A
Winker
Robert
R
Schmut
Otto
O
Paulweber
Bernhard
B
Iglseder
Bernhard
B
Renner
Wilfried
W
Wiesbauer
Martina
M
Aigner
Irene
I
Santic
Danijela
D
Zimmermann
Franz A
FA
Mayr
Johannes A
JA
Sperl
Wolfgang
W
D000368:Aged; D000369:Aged, 80 and over; D001317:Austria; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
D004272:DNA, Mitochondrial