Mitochondrial DNA haplogroup T is associated with coronary artery disease and diabetic retinopathy: a case control study

Barbara Kofler,Johannes A Mayr,Franz A Zimmermann,Bernhard Iglseder,Wilfried Renner,Robert Winker,Danijela Santic,Waltraud Eder,Anton Haas,Wolfgang Sperl,Bernhard Paulweber,Otto Schmut,Richard Maier,Martina Wiesbauer,Edith E Mueller,Martin Weger,Irene Aigner,Olaf Stanger

doi:10.1186/1471-2350-10-35

Abstract

BackgroundThere 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.MethodsThis 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.ResultsHaplogroup 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).ConclusionOur data indicate that the mtDNA haplogroup T is associated with CAD and diabetic retinopathy in Middle European Caucasian populations.

Highlights

There is strong and consistent evidence that oxidative stress is crucially involved in the development of atherosclerotic vascular disease
We aimed to investigate the association of mitochondrial DNA (mtDNA) haplogroups with coronary artery disease (CAD) as well as diabetic retinopathy
Further adjustment for possible confounders revealed that the strong association between haplogroup T and CAD was not explained by differences in age, sex, hypertension, body mass index, or smoking status (Table 3)

Summary

Introduction

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. Mitochondria are the primary source of endogenous reactive oxygen species (ROS), generated through oxidative phosphorylation (OXPHOS) as a by-product of ATP synthesis. 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. Four of the enzymatic complexes that constitute the oxidative phosphorylation system (OXPHOS) are partially encoded by the mtDNA. Rare pathogenic mutations of the mtDNA, that either impair mitochondrial protein synthesis or impair proteins encoded by the mtDNA have been associated with more than 70 human diseases [2]

Objectives

Methods

Results

Discussion

Conclusion