Association between large detectable clonal mosaicism and type 2 diabetes with vascular complications
Association between large detectable clonal mosaicism and type 2 diabetes with vascular complications
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DOI：
10.1038/ng.2700
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发表时间：
2013-09-01
期刊：
影响因子：
30.8
通讯作者：
Froguel, Philippe
中科院分区：
文献类型：
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作者：
Bonnefond, Amelie;Skrobek, Boris;Froguel, Philippe
大型染色体克隆镶嵌事件（CMEs）被认为与衰老（1 - 3）有关，并可预测癌症（2，3）。2型糖尿病（T2D）被概念化为一种加速衰老的疾病（4 - 6），且与较高的癌症患病率相关（7 - 11）。在此，我们旨在评估2型糖尿病与血液中CME发生之间的关联。我们使用DNA芯片评估了7659人（包括2208名2型糖尿病患者）中CME的存在情况。发现CME发生与2型糖尿病之间存在显著关联（优势比（OR）= 5.3；P = 5.1×10⁻⁵），当我们仅考虑非肥胖的2型糖尿病患者时，这种关联更强（OR = 5.6；P = 4.9×10⁻⁵）。值得注意的是，患有2型糖尿病的CME携带者血管并发症的患病率高于无CME的2型糖尿病患者（分别为71.4%对37.1%；P = 7.7×10⁻⁴）。在CME携带者中，我们发现异常细胞的百分比在6年内有所增加（P = 8.60×10⁻³）。总之，鉴于CME携带者患癌症的风险增加（2，3），我们的研究结果可能对重度2型糖尿病患者具有深远的临床意义。
Large chromosomal clonal mosaic events (CMEs) have been suggested to be linked to aging(1-3) and to predict cancer(2,3). Type 2 diabetes (T2D) has been conceptualized as an accelerated-aging disease(4-6) and is associated with higher prevalence of cancers(7-11). Here we aimed to assess the association between T2D and CME occurrence in blood. We evaluated the presence of CMEs in 7,659 individuals (including 2,208 with T2D) using DNA arrays. A significant association between CME occurrence and T2D was found (odds ratio (OR) = 5.3; P = 5.1 x 10(-5)) and was stronger when we only considered non-obese individuals with T2D (OR = 5.6; P = 4.9 x 10(-5)). Notably, CME carriers with T2D had higher prevalence of vascular complications than non-carriers with T2D (71.4% versus 37.1%, respectively; P = 7.7 x 10(-4)). In CME carriers, we found an increase in the percentage of abnormal cells over 6 years (P = 8.60 x 10(-3)). In conclusion, given the increased risk of cancer in CME carriers(2,3), our results may have profound clinical implications in patients with severe T2D.