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

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• dc.contributor.author Papandreou, Christopher
• dc.contributor.author Li, Jun
• dc.contributor.author Liang, Liming
• dc.contributor.author Bulló, Mònica
• dc.contributor.author Zheng, Yan
• dc.contributor.author Ruiz-Canela, Miguel
• dc.contributor.author Yu, Edward
• dc.contributor.author Guasch Ferré, Marta
• dc.contributor.author Razquin, Cristina
• dc.contributor.author Clish, Clary B.
• dc.contributor.author Corella, Dolores
• dc.contributor.author Estruch, Ramón
• dc.contributor.author Ros, Emilio
• dc.contributor.author Fitó Colomer, Montserrat
• dc.contributor.author Arós, Fernando
• dc.contributor.author Serra-Majem, Luis
• dc.contributor.author Rosique-Esteban, Nuria
• dc.contributor.author Martínez-González, Miguel Ángel, 1957-
• dc.contributor.author Hu, Frank B.
• dc.contributor.author Salas-Salvadó, Jordi
• dc.date.accessioned 2020-04-22T06:54:07Z
• dc.date.available 2020-04-22T06:54:07Z
• dc.date.issued 2019
• dc.description.abstract 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.
• dc.description.sponsorship This study was supported by research grant R01-DK-102896 from the National Institutes of Health. The Prevención con DietaMediterránea (PREDIMED) trial was supported by the official funding agency for biomedical research of the Spanish government, the Instituto de Salud Carlos III, through grants provided to research networks specifically developed for the trial [grant RTIC G03/140 (to Ramón Estruch); grant RTIC RD 06/0045 (to Miguel A. Martínez-González)] and through the Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición and by grants from Centro Nacional de Investigaciones Cardiovasculares (grant CNIC 06/2007), the Fondo de Investigación Sanitaria Fondo Europeo de Desarrollo Regional (grants PI04–2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505, and PI13/00462), the Ministerio de Ciencia e Innovación (grants AGL-2009–13906-C02 and AGL2010–22319-C03), the Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (grant PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (grants ACOMP06109, GVA-COMP2010–181, GVACOMP2011–151, CS2010-AP-111, and CS2011-AP-042), and the Regional Government of Navarra (grant P27/2011). Genotyping of the TCF7L2-rs7903146 polymorphism was supported by PROMETEO17/2017 from the Generalitat Valenciana, and 538/U/2016 from Fundacio la Marato-TV3. Dr. Christopher Papandreou was supported by a postdoctoral fellowship granted by the Autonomous Government of Catalonia (PERIS 2016-2020 INCORPORACIÓ DE CIENTÍFICAS I TECNÒLEGS, SLT002/0016/00428). Dr Marta Guasch-Ferré was supported by a postdoctoral fellowship granted by the Lilly Foundation European Association of Diabetes (EASD) through the Institut d’Investigacions Sanitàries Pere i Virgili (IISPV), Tarragona, Spain. The authors are indebted to George A. Fragkiadakis (Department of Nutrition & Dietetics, Technological Education Institute of Crete, Greece) for his intellectual contributions to this manuscript.
• dc.format.mimetype application/pdf
• dc.identifier.citation Papandreou C, Li J, Liang L, Bulló M, Zheng Y, Ruiz-Canela M, et al. Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism. Sci Rep. 2019 Feb 27; 9(1):2892. DOI: 10.1038/s41598-019-39441-6
• dc.identifier.doi http://dx.doi.org/10.1038/s41598-019-39441-6
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/44303
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/AGL2009–13906-C02
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/AGL2010–22319-C03
• dc.rights Copyright © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Metabòlits
• dc.subject.other Diabetis
• dc.title Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion