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

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

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.

引用

页数：11

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