Mitochondrial DNA Backgrounds Might Modulate Diabetes Complications Rather than T2DM as a Whole
Mitochondrial DNA Backgrounds Might Modulate Diabetes Complications Rather than T2DM as a Whole
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DOI：
10.1371/journal.pone.0021029
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发表时间：
2011-06-09
期刊：
影响因子：
3.7
通讯作者：
Torroni, Antonio
中科院分区：
文献类型：
--
作者：
Achilli, Alessandro;Olivieri, Anna;Torroni, Antonio
线粒体功能障碍与罕见和常见的2型糖尿病（T2DM）有关。此外，罕见的线粒体DNA （mtDNA）突变已被证明是T2DM发病的原因。到目前为止，许多研究已经调查了mtDNA变异可能影响T2DM风险的可能性，然而，即使在相关人群中，单倍群关联也很少被复制，可能是由于单倍群分辨率水平不足。mtDNA变异对糖尿病并发症的影响也被提出。然而，还需要进一步的研究来评估线粒体在T2DM和相关并发症中的作用。为了验证线粒体基因组对糖尿病及其并发症影响的假设，我们对来自意大利中部地区人群（Marche）的466名T2DM患者和438名对照者的mtdna进行了基因分型。基于最新的mtDNA系统发育，所有904个样本被划分为57个不同的线粒体亚单倍群，从而达到前所未有的分辨率水平。考虑到表型和临床变量的潜在影响，我们评估了在确定的单倍群中发生T2DM或其并发症的易感性是否存在差异。MtDNA背景，即使是基于精确的单倍群分类，似乎在T2DM的发生中没有发挥作用，尽管可能对欧洲常见的单倍群H1有保护作用，其中包含MTRNR2基因的G3010A转位。相反，我们的数据表明，不同的线粒体单倍群与特定糖尿病并发症的风险增加显著相关：H（最常见的欧洲单倍群）与视网膜病变有关，H3与神经病变有关，U3与肾病有关，V与肾衰竭有关。
Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure.