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Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population.

ABSTRACT: OBJECTIVE: Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet. RESEARCH DESIGN AND METHODS: A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events. RESULTS: The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 [95% CI 1.62-2.17] for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 [95% CI 1.36-6.19]; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 [95% CI 0.49-1.87]; P = 0.892 for TT compared with CC). CONCLUSIONS: Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.

SUBMITTER: Corella D

PROVIDER: S-EPMC3816851 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population.

Corella Dolores D Carrasco Paula P Sorlí Jose V JV Estruch Ramón R Rico-Sanz Jesús J Martínez-González Miguel Ángel MÁ Salas-Salvadó Jordi J Covas M Isabel MI Coltell Oscar O Arós Fernando F Lapetra José J Serra-Majem Lluís L Ruiz-Gutiérrez Valentina V Warnberg Julia J Fiol Miquel M Pintó Xavier X Ortega-Azorín Carolina C Muñoz Miguel Ángel MÁ Martínez J Alfredo JA Gómez-Gracia Enrique E González José I JI Ros Emilio E Ordovás José M JM

Diabetes care 20130813 11

<h4>Objective</h4>Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet.<h4>Research design and methods</h4>A randomized tria ...[more]

PMID: 23942586

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Project description:BackgroundTCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects.Methods and resultstwo populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95%CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004).Conclusionsrs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets.Clinical trial registration informationMEDICINE, ANGIOPLASTY, OR SURGERY STUDY (MASS II): Unique identifier: ISRCTN66068876.

Project description:BackgroundThere are racial and ethnic differences in the prevalence of gestational diabetes mellitus (GDM). Prior meta-analyses included small samples and very limited non-Caucasian populations. Studies to determine the relationship between transcription factor 7 like-2 (TCF7L2) rs7903146 polymorphism and risk of GDM in Hispanics/Latinos are recently available. The present meta-analysis was to estimate the impact of allele variants of TCF7L2 rs7903146 polymorphism on GDM susceptibility in overall population and racial/ethnic subgroups.MethodsLiterature was searched in multiple databases including PubMed, Web of Science, EMBASE (Ovid SP), Airiti Library, Medline Complete, and ProQuest up to July 2015. Allelic frequency for TCF7L2 rs7903146 polymorphism in GDM and control subjects was extracted and statistical analysis was performed using Comprehensive Meta-Analysis (CMA) 2.0 statistical software. The association between TCF7L2 rs7903146 polymorphism and GDM risk was assessed by pooled odd ratios (ORs) using five gene models (dominant, recessive, homozygote, heterozygote, and allele). Stratified analysis based on race/ethnicity was also conducted. The between-study heterogeneity and contribution of each single study to the final result was tested by Cochran Q test and sensitivity analyses, respectively. Publication bias was evaluated using Egger's linear regression test.ResultsA total of 16 studies involving 4,853 cases and 10,631 controls were included in this meta-analysis. Significant association between the T-allele of rs7903146 and GDM risk was observed under all genetic models, dominant model (OR = 1.44, 95% CI = 1.19-1.74), recessive model (OR = 1.35, 95% CI = 1.08-1.70), heterozygous model (OR = 1.31, 95% CI = 1.12-1.53), homozygous model (OR = 1.67, 95% CI = 1.31-2.12), and allele model (OR = 1.31, 95% CI = 1.12-1.53). Stratified analysis by race/ethnicity showed a statistically significant association between rs7903146 polymorphism and susceptibility to GDM under homozygous genetic model (TT versus CC) among whites, Hispanics/Latinos and Asians. Sensitivity analysis showed that the overall findings were robust to potentially influential decisions of the 16 studies included. No significant evidence for publication bias was observed in this meta-analysis for overall studies and subgroup studies.ConclusionsThis meta-analysis showed that the T allele of TCF7L2 rs7903146 polymorphism was associated with susceptibility of GDM in overall population in white, Hispanic/Latino and Asian sub-groups. Asians with homozygous TT allele of rs7903146 polymorphism have highest risk of GDM (OR = 2.08) followed by Hispanics/Latinos (OR = 1.80) and whites (OR = 1.51). The highest and lowest frequency of T allele of rs7903146 was found in Malaysia and South Korea, respectively. Future studies are needed to profile genetic risk for GDM among high risk Asian and Pacific Islander subgroups.

Project description:AimsTo investigate whether metabolic signature composed of multiple plasma metabolites can be used to characterize adherence and metabolic response to the Mediterranean diet and whether such a metabolic signature is associated with cardiovascular disease (CVD) risk.Methods and resultsOur primary study cohort included 1859 participants from the Spanish PREDIMED trial, and validation cohorts included 6868 participants from the US Nurses' Health Studies I and II, and Health Professionals Follow-up Study (NHS/HPFS). Adherence to the Mediterranean diet was assessed using a validated Mediterranean Diet Adherence Screener (MEDAS), and plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry. We observed substantial metabolomic variation with respect to Mediterranean diet adherence, with nearly one-third of the assayed metabolites significantly associated with MEDAS (false discovery rate < 0.05). Using elastic net regularized regressions, we identified a metabolic signature, comprised of 67 metabolites, robustly correlated with Mediterranean diet adherence in both PREDIMED and NHS/HPFS (r = 0.28-0.37 between the signature and MEDAS; P = 3 × 10-35 to 4 × 10-118). In multivariable Cox regressions, the metabolic signature showed a significant inverse association with CVD incidence after adjusting for known risk factors (PREDIMED: hazard ratio [HR] per standard deviation increment in the signature = 0.71, P < 0.001; NHS/HPFS: HR = 0.85, P = 0.001), and the association persisted after further adjustment for MEDAS scores (PREDIMED: HR = 0.73, P = 0.004; NHS/HPFS: HR = 0.85, P = 0.004). Further genome-wide association analysis revealed that the metabolic signature was significantly associated with genetic loci involved in fatty acids and amino acids metabolism. Mendelian randomization analyses showed that the genetically inferred metabolic signature was significantly associated with risk of coronary heart disease (CHD) and stroke (odds ratios per SD increment in the genetically inferred metabolic signature = 0.92 for CHD and 0.91 for stroke; P < 0.001).ConclusionsWe identified a metabolic signature that robustly reflects adherence and metabolic response to a Mediterranean diet, and predicts future CVD risk independent of traditional risk factors, in Spanish and US cohorts.

Dataset Information

Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population.

Publications

Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population.

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