6533b823fe1ef96bd127f6cd

RESEARCH PRODUCT

Polymorphism of the Transcription Factor 7-Like 2 Gene (TCF7L2) Interacts with Obesity on Type-2 Diabetes in the PREDIMED Study Emphasizing the Heterogeneity of Genetic Variants in Type-2 Diabetes Risk Prediction: Time for Obesity-Specific Genetic Risk Scores

Laura QuilesLaura QuilesJosé V SorlíJosé V. SorlíMiquel FiolFernando ArósManuel Ortega-calvoJordi Salas-salvadóJosep BasoraRamon EstruchRamon EstruchEmilio RosEmilio RosOlga PortolésOlga PortolésOscar ColtellOscar ColtellDolores CorellaDolores CorellaMiguel ÁNgel Martínez-gonzálezMiguel ÁNgel Martínez-gonzálezMontserrat FitóOlga CastañerLluis Serra-majemLluis Serra-majemJavier Díez EspinoJavier Díez EspinoJose M. OrdovasJose M. OrdovasJose M. OrdovasEnrique Gómez-graciaEnrique Gómez-gracia

subject

0301 basic medicineOncologyMaleobesityendocrine system diseasesType 2 diabetestype-2 diabetesTranscription Factor 7-Like 2Dieta mediterrània0302 clinical medicineNutrigenomicsRisk FactorsPrevalenceTCF7L2-predictive valueDiseaseLongitudinal StudiesProspective StudiesGenetic riskGeneticsAged 80 and overINSULIN-RESISTANCEBioquímica y tecnologíaNutrition and DieteticsDiabetisIncidenceMiddle AgedTraitsMEDITERRANEAN DIETBiochemistry and technologyObesitatTRIALFemalelcsh:Nutrition. Foods and food supplyTranscription Factor 7-Like 2 ProteinAdultGenetic Markersmedicine.medical_specialtyendocrine systemPopulationBODY-FATlcsh:TX341-641030209 endocrinology & metabolismMASSBioquímica i biotecnologiaArticleAssociation03 medical and health sciencesGenetic HeterogeneityPredictive Value of TestsInternal medicineDiabetes mellitusmedicineHumansGenetic Predisposition to DiseaseGeneAgedPolymorphism Geneticbusiness.industryCommon variantsPreventionnutritional and metabolic diseasesGenetic VariationPREDIMED studymedicine.disease2072-6643WeightPredimedObesityTCF7L2TCF7L2; type-2 diabetes; obesity; T2D-genetic risk scores; TCF7L2-predictive value; PREDIMED study030104 developmental biologyDiabetes Mellitus Type 2Susceptibility locibusinessTCF7L2T2D-genetic risk scoresFood Science

description

Nutrigenetic studies analyzing gene-diet interactions of the TCF7L2-rs7903146 C > T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C > T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED participants at baseline and longitudinally (8.7 years maximum follow-up). Obesity significantly interacted with the TCF7L2-rs7903146 on T2D prevalence, associations being greater in non-obese subjects. Accordingly, we prospectively observed in non-T2D subjects (n = 3607) that its association with T2D incidence was stronger in non-obese (HR: 1.81; 95% CI: 1.13-2.92, p = 0.013 for TT versus CC) than in obese subjects (HR: 1.01; 95% CI: 0.61-1.66; p = 0.979; p-interaction = 0.048). Accordingly, TCF7L2-PV was higher in non-obese subjects. Additionally, we created obesity-specific GRS with ten T2D-polymorphisms and demonstrated for the first time their higher strata-specific PV. In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D.

yearjournalcountryeditionlanguage
2016-12-01
10.3390/nu8120793https://hdl.handle.net/10668/19310