Interaction between HNF4A polymorphisms and physical activity in relation to type 2 diabetes-related traits: Results from the Quebec Family Study

Stephanie-May, Ruchat; W, John; Rankinen, Tuomo; Bouchard, Claude; Vohl, Marie‐Claude; Pérusse, L

doi:10.1016/j.diabres.2009.03.012

Cited by 10 publications

(11 citation statements)

References 49 publications

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“…Interestingly, sex, adiponectin, interleukin-6 levels and lifestyle habits were not selected as markers with a particularly important contribution to the disease by the random forest model. As to adiponectin and lifestyle habits, one explanation might be that age, waist circumference, leptin levels and some of the risk alleles cover much of the risk common to the preselected study population [21], [61]–[66].…”

Section: Discussionmentioning

confidence: 99%

The Association of Genetic Markers for Type 2 Diabetes with Prediabetic Status - Cross-Sectional Data of a Diabetes Prevention Trial

et al. 2013

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ObjectiveTo investigate the association of risk alleles for type 2 diabetes with prediabetes accounting for age, anthropometry, inflammatory markers and lifestyle habits.DesignCross-sectional study of 129 men and 157 women of medium-sized companies in northern Germany in the Delay of Impaired Glucose Tolerance by a Healthy Lifestyle Trial (DELIGHT).MethodsBesides established risk factors, 41 single nucleotide polymorphisms (SNPs) that have previously been found to be associated with type 2 diabetes were analyzed. As a nonparametric test a random forest approach was used that allows processing of a large number of predictors. Variables with the highest impact were entered into a multivariate logistic regression model to estimate their association with prediabetes.ResultsIndividuals with prediabetes were characterized by a slightly, but significantly higher number of type 2 diabetes risk alleles (42.5±4.1 vs. 41.3±4.1, p = 0.013). After adjustment for age and waist circumference 6 SNPs with the highest impact in the random forest analysis were associated with risk for prediabetes in a logistic regression model. At least 5 of these SNPs were positively related to prediabetic status (odds ratio for prediabetes 1.57 per allele (Cl 1.21–2.10, p = 0.001)).ConclusionsThis explorative analysis of data of DELIGHT demonstrates that at least 6 out of 41 genetic variants characteristic of individuals with type 2 diabetes may also be associated with prediabetes. Accumulation of these risk alleles may markedly increase the risk for prediabetes. However, prospective studies are required to corroborate these findings and to demonstrate the predictive value of these genetic variants for the risk to develop prediabetes.

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Section: Discussionmentioning

confidence: 99%

The Association of Genetic Markers for Type 2 Diabetes with Prediabetic Status - Cross-Sectional Data of a Diabetes Prevention Trial

et al. 2013

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“…A total of 49 eligible reports investigated the association between SNPs and the gAUC after an OGTT in 39 different cohorts, i.e., Quebec Family Study [ 12 , 13 , 14 , 15 , 16 , 17 ], Amish Family Diabetes Study [ 18 , 19 ], Ely Study [ 20 ], Tübingen Family Study (TÜF) [ 21 ], European Atherosclerosis Research Study (EARS II) [ 22 , 23 ], Sapphire Study [ 24 ], Metabolic Intervention Cohort Kiel (MICK) [ 25 , 26 ], European Network on Functional Genomics of Type 2 Diabetes (EUGENE2) [ 27 , 28 ], Metabolic Syndrome in Men (METSIM) [ 28 ], Metabolic Syndrome Berlin Potsdam Study (MESYBEPO) [ 29 ], Lifestyle Intervention in a General Population for Prevention of Ischaemic Heart Disease (Inter99) [ 30 , 31 ], Berlin Ernährung Geschwister Study (BErG-Study) [ 32 ], and further 27 cohorts without a specific study name [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ...…”

Section: Resultsmentioning

confidence: 99%

“…In one study, a glucose amount of either 50 or 75 g was used without any justification [ 42 ]. While in most of the reports, the duration of the OGTT lasted 120 min [ 20 , 21 , 22 , 23 , 24 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 36 , 37 , 38 , 39 , 41 , 43 , 44 , 45 , 47 , 48 , 50 , 52 , 53 , 54 , 56 , 57 , 58 , 59 , 60 ] or 180 min [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 35 , 40 , 42 , 49 , 51 , 55 ], in either two reports the OGTT was performed over 240 min [ 25 , 26 ] or 300 min [ 34 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

Association between Genotype and the Glycemic Response to an Oral Glucose Tolerance Test: A Systematic Review

et al. 2023

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The inter-individual variability of metabolic response to foods may be partly due to genetic variation. This systematic review aims to assess the associations between genetic variants and glucose response to an oral glucose tolerance test (OGTT). Three databases (PubMed, Web of Science, Embase) were searched for keywords in the field of genetics, OGTT, and metabolic response (PROSPERO: CRD42021231203). Inclusion criteria were available data on single nucleotide polymorphisms (SNPs) and glucose area under the curve (gAUC) in a healthy study cohort. In total, 33,219 records were identified, of which 139 reports met the inclusion criteria. This narrative synthesis focused on 49 reports describing gene loci for which several reports were available. An association between SNPs and the gAUC was described for 13 gene loci with 53 different SNPs. Three gene loci were mostly investigated: transcription factor 7 like 2 (TCF7L2), peroxisome proliferator-activated receptor gamma (PPARγ), and potassium inwardly rectifying channel subfamily J member 11 (KCNJ11). In most reports, the associations were not significant or single findings were not replicated. No robust evidence for an association between SNPs and gAUC after an OGTT in healthy persons was found across the identified studies. Future studies should investigate the effect of polygenic risk scores on postprandial glucose levels.

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“…Significant relationship between the genetic variant rs16834817 in MYLK and coronary artery disease was also established in this cohort. The rs745975 C>T HNF4α (identified in baseline gene expression analysis; Supplemental Table 3) SNP is associated with S i and glucose tolerance; both associations are modified by physical activity (31). This common variant has also previously been linked to serum lipid levels (37).…”

Section: Discussionmentioning

confidence: 99%

“…Heritability estimates for insulin action on glucose homeostasis in individuals of European ancestry range between 25%-44% (31). Genetic variants account for small to modest amounts of trait variability (29).…”

Section: Introductionmentioning

confidence: 99%

Pyruvate Dehydrogenase Phosphatase Regulatory Gene Expression Correlates with Exercise Training Insulin Sensitivity Changes

Barberio

Huffman

Giri

et al. 2016

Medicine &Amp; Science in Sports &Amp; Exercise

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Purpose Whole body insulin sensitivity (Si) typically improves following aerobic exercise training; however, individual responses can be highly variable. The purpose of this study was to use global gene expression to identify skeletal muscle genes that correlate with exercise-induced Si changes. Methods Longitudinal cohorts from the Studies of Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) were utilized as Discovery (Affymetrix) and Confirmation (Illumina) of vastus lateralis gene expression profiles. Discovery (n=39; 21 men) and Confirmation (n=42; 19 men) cohorts were matched for age (52 ± 8 vs. 51 ± 10 yr), BMI (30.4 ± 2.8 vs. 29.7 ± 2.8 kg*m-2), and VO2max (30.4 ± 2.8 vs. 29.7 ± 2.8 mL/kg/min). Si was determined via intravenous glucose tolerance test pre- and post-training. Pearson product-moment correlation coefficients determined relationships between a) baseline and b) training-induced changes in gene expression and %ΔSi after training. Results Expression of 2454 (Discovery) and 1778 genes (Confirmation) at baseline were significantly (P<0.05) correlated to %ΔSi; 112 genes overlapped. Pathway analyses identified Ca2+-signaling-related transcripts in this 112-gene list. Expression changes of 1384 (Discovery) and 1288 genes (Confirmation) following training were significantly (P<0.05) correlated to % ΔSi; 33 genes overlapped, representing contractile apparatus of skeletal and smooth muscle genes. Pyruvate dehydrogenase phosphatase regulatory subunit (PDPR) expression at baseline (p=0.01, r=0.41) and post-training (p=0.01, r=0.43) were both correlated with %ΔSi. Conclusion Exercise-induced adaptations in skeletal muscle Si are related to baseline levels of Ca+2-regulating transcripts, which may prime the muscle for adaptation. Relationships between %ΔSi and PDPR, a regulatory subunit of the pyruvate dehydrogenase complex, indicate that the Si response is strongly related to key steps in metabolic regulation.

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Interaction between HNF4A polymorphisms and physical activity in relation to type 2 diabetes-related traits: Results from the Quebec Family Study

Cited by 10 publications

References 49 publications

The Association of Genetic Markers for Type 2 Diabetes with Prediabetic Status - Cross-Sectional Data of a Diabetes Prevention Trial

The Association of Genetic Markers for Type 2 Diabetes with Prediabetic Status - Cross-Sectional Data of a Diabetes Prevention Trial

Association between Genotype and the Glycemic Response to an Oral Glucose Tolerance Test: A Systematic Review

Pyruvate Dehydrogenase Phosphatase Regulatory Gene Expression Correlates with Exercise Training Insulin Sensitivity Changes

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