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

被引:105
作者
Bonnefond, Amelie [1 ,2 ,3 ]
Skrobek, Boris [1 ,2 ,3 ]
Lobbens, Stephane [1 ,2 ,3 ]
Eury, Elodie [1 ,2 ,3 ]
Thuillier, Dorothee [1 ,2 ,3 ]
Cauchi, Stephane [1 ,2 ,3 ]
Lantieri, Olivier [4 ]
Balkau, Beverley [5 ,6 ]
Riboli, Elio [7 ]
Marre, Michel [8 ,9 ]
Charpentier, Guillaume [10 ]
Yengo, Loic [1 ,2 ,3 ]
Froguel, Philippe [1 ,2 ,3 ,11 ,12 ]
机构
[1] CNRS, Lille Pasteur Inst, UMR 8199, Lille, France
[2] Univ Lille, Lille, France
[3] EGID, Lille, France
[4] Inst Inter Reg Sante IRSA, La Riche, France
[5] INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France
[6] Univ Paris Sud, Villejuif, France
[7] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England
[8] Bichat Claude Bernard Univ Hosp, AP HP, Dept Endocrinol Diabetol & Nutr, Paris, France
[9] Univ Paris 07, INSERM U695, Paris, France
[10] Corbeil Essonnes Hosp, Dept Endocrinol & Diabetol, Essonnes, France
[11] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Publ Hlth, Dept Genom Common Dis, London, England
[12] QBRI, Doha, Qatar
关键词
GENETIC-VARIATION; DRUG DISCOVERY; GENOME; CANCER; OBESITY; INSULIN; AGE;
D O I
10.1038/ng.2700
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
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.
引用
收藏
页码:1040 / +
页数:6
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