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

Identifier:  imarina:4239656

Handle: https://hdl.handle.net/20.500.11797/imarina4239656

Authors:  Papandreou, Christopher; Li, Jun; Liang, Liming; Bullo, Monica; Zheng, Yan; Ruiz-Canela, Miguel; Yu, Edward; Guasch-Ferre, Marta; Razquin, Cristina; Clish, Clary; Corella, Dolores; Estruch, Ramon; Ros, Emilio; Fito, Montserrat; Aros, Fernando; Serra-Majem, Lluis; Rosique, Nuria; Martinez-Gonzalez, Miguel A; Hu, Frank B; Salas-Salvado, Jordi

Abstract:
© 2019, The Author(s). 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.