Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism

被引:30
作者
Papandreou, Christopher [1 ,2 ]
Li, Jun [3 ]
Liang, Liming [4 ,5 ]
Bullo, Monica [1 ,2 ]
Zheng, Yan [3 ]
Ruiz-Canela, Miguel [2 ,6 ]
Yu, Edward [3 ]
Guasch-Ferre, Marta [1 ,2 ,3 ]
Razquin, Cristina [2 ,6 ]
Clish, Clary [7 ]
Corella, Dolores [2 ,8 ]
Estruch, Ramon [2 ,9 ]
Ros, Emilio [2 ,10 ]
Fito, Montserrat [2 ,11 ]
Aros, Fernando [2 ,12 ]
Serra-Majem, Lluis [2 ,13 ]
Rosique, Nuria [1 ,2 ]
Martinez-Gonzalez, Miguel A. [2 ,3 ,6 ]
Hu, Frank B. [3 ,4 ,5 ,14 ,15 ]
Salas-Salvado, Jordi [1 ,2 ]
机构
[1] Rovira & Virgili Univ, Inst Invest Sanitaria Pere Virgili, Human Nutr Unit, Fac Med & Hlth Sci, Reus, Spain
[2] Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr CIBERObn, Madrid, Spain
[3] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA
[4] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
[5] Harvard TH Chan Sch Publ Hlth, Dept Stat, Boston, MA USA
[6] Univ Navarra, Dept Prevent Med & Publ Hlth, Pamplona, Spain
[7] Broad Inst MIT & Harvard Univ, Cambridge, MA USA
[8] Univ Valencia, Dept Prevent Med, Valencia, Spain
[9] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi Sunyer IDI BAPS, Dept Internal Med,Dept Endocrinol & Nutr, Barcelona, Spain
[10] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi Sunyer IDI BAPS, Lipid Clin,Dept Endocrinol & Nutr, Barcelona, Spain
[11] Hosp del Mar, Cardiovasc & Nutr Res Grp, Inst Recerca, Barcelona, Spain
[12] Univ Hosp Alava, Dept Cardiol, Vitoria, Spain
[13] Univ Las Palmas Gran Canaria, Dept Clin Sci, Las Palmas Gran Canaria, Spain
[14] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, 75 Francis St, Boston, MA 02115 USA
[15] Harvard Med Sch, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
ADENOSINE; ALLANTOIN;
D O I
10.1038/s41598-019-39441-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of the TCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated.
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页数:11
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