Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
PLoS One. 2011 Jan 26;6(1):e16455. doi: 10.1371/journal.pone.0016455.
The pivotal role of mitochondria in energy production and free radical generation suggests that the mitochondrial genome could have an important influence on the expression of multifactorial age related diseases. Substitution of T to C at nucleotide position 16189 in the hypervariable D-loop of the control region (CR) of mitochondrial DNA (mtDNA) has attracted research interest because of its suspected association with various multifactorial diseases. The aim of the present study was to compare the frequency of this polymorphism in the CR of mtDNA in patients with coronary artery disease (CAD, n = 482) and type 2 diabetes mellitus (T2DM, n = 505) from two study centers, with healthy individuals (n = 1481) of Middle European descent in Austria.
CR polymorphisms and the nine major European haplogroups were identified by DNA sequencing and primer extension analysis, respectively. Frequencies and Odds Ratios for the association between cases and controls were calculated. Compared to healthy controls, the prevalence of T16189C was significantly higher in patients with CAD (11.8% vs 21.6%), as well as in patients with T2DM (11.8% vs 19.4%). The association of CAD, but not the one of T2DM, with T16189C remained highly significant after correction for age, sex and body mass index (BMI) and was independent of the two study centers.
Our results show for the first time a significant association of T16189C with CAD in a Middle European population. As reported in other studies, in patients with T2DM an association with T16189C in individuals of European decent remains questionable.
线粒体在能量产生和自由基生成中的关键作用表明，线粒体基因组可能对多因素与年龄相关疾病的表达有重要影响。核苷酸位置 16189 处的 T 到 C 取代在控制区（CR）的线粒体 DNA（mtDNA）的高变区 D-环中引起了研究兴趣，因为其与各种多因素疾病的可疑关联。本研究的目的是比较来自两个研究中心的冠心病（CAD，n = 482）和 2 型糖尿病（T2DM，n = 505）患者与奥地利中欧洲裔健康个体（n = 1481）mtDNA 的 CR 中这种多态性的频率。
通过 DNA 测序和引物延伸分析分别鉴定 CR 多态性和 9 个主要欧洲单倍群。计算病例与对照之间关联的频率和优势比。与健康对照相比，CAD 患者（11.8%对 21.6%）和 T2DM 患者（11.8%对 19.4%）中 T16189C 的患病率明显更高。在校正年龄、性别和体重指数（BMI）后，CAD 的相关性，而不是 T2DM 的相关性，与 T16189C 仍然高度显著，并且与两个研究中心无关。
我们的结果首次显示 T16189C 与中欧洲人群中的 CAD 存在显著相关性。与其他研究报告的一样，在欧洲裔个体中，T2DM 患者与 T16189C 的关联仍存在疑问。
