Association between large detectable clonal mosaicism and type 2 diabetes with vascular complications

作者:Bonnefond Amelie; Skrobek Boris; Lobbens Stephane; Eury Elodie; Thuillier Dorothee; Cauchi Stephane; Lantieri Olivier; Balkau Beverley; Riboli Elio; Marre Michel; Charpentier Guillaume; Yengo Loic; Froguel Philippe*
来源:Nature Genetics, 2013, 45(9): 1040-+.
DOI:10.1038/ng.2700

摘要

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.

  • 出版日期2013-9