The<i>FOXO3A</i>rs2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-<i>FOXO3A</i>mRNA Expression in Twins

Banasik, Karina; Ribel‐Madsen, Rasmus; Gjesing, Anette P.; Wegner, Lise; Andersson, Åsa; Poulsen, Pernille; Borglykke, Anders; Witte, Daniel R.; Pedersen, Oluf; Hansen, Torben; Vaag, Allan

doi:10.1210/jc.2010-0881

Cited by 47 publications

(50 citation statements)

References 19 publications

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“…The most familiar FOXO3A intronic SNP rs2802292 is characterized by a G to T transversion. A twin cohort study suggested that carriers of the minor G allele of rs2802292 showed reduced fasting plasma insulin and lower incremental area under the curve 0–120 min for insulin following oral glucose loading compared with non-carriers, indicating that the minor G allele was associated with enhanced peripheral and hepatic insulin sensitivity, possibly mediated through increased FOXO3A mRNA expression 25. Improved insulin sensitivity has been considered as a feature of long-lived individuals.…”

Section: Discussionmentioning

confidence: 99%

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

et al. 2014

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Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10–1.69, P = 0.005; OR = 1.20, 95% CI = 1.04–1.37, P = 0.01; OR = 1.27, 95% CI = 1.10–1.46, P = 0.001; OR = 1.14, 95% CI = 1.01–1.27 and OR = 1.24, 95% CI = 1.07–1.43, P = 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33–1.79, P < 0.001; OR = 1.38, 95% CI = 1.15–1.66, P = 0.001; and OR = 1.39, 95% CI = 1.15–1.67, P = 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

et al. 2014

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“…But whether these variants also play a role in the pathogenesis of type 2 diabetes has not been yet studied. Additionally, one study also reported that the minor allele of the SNP rs2802292 in FOXO3 is associated with improved peripheral and hepatic insulin sensitivity in twins (Banasik et al, 2011). In this study we have carried out a detailed case control analysis of common variants in FOXO3 using haplotype tagging SNP approach for association with type 2 diabetes and related biochemical parameters.…”

Section: Introductionmentioning

confidence: 99%

Association analysis of common variants in FOXO3 with type 2 diabetes in a South Indian Dravidian population

Nair

Sugunan

Kumar

et al. 2012

Gene

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“…Functional DAF-16, the worm FOXO transcription factor, has been demonstrated to be required for the longevity of many of the lifespan enhancing mutations [39]; [40]. Interestingly, human population studies have revealed an association between single nucleotide polymorphisms (SNPs) in human FOXO3 and human lifespan extension [41]; [42] [43]; [44]) and the strength of the association appears to increase with age [45]. Therefore, FOXO3 appears to be a candidate longevity gene in humans and thus demonstrates how work in the humble nematode worm can inform on the biology of human ageing.…”

Section: Wormsmentioning

confidence: 99%

Animal and human models to understand ageing

2016

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Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing.

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TheFOXO3Ars2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-FOXO3AmRNA Expression in Twins

Cited by 47 publications

References 19 publications

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

Association analysis of common variants in FOXO3 with type 2 diabetes in a South Indian Dravidian population

Animal and human models to understand ageing

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