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Epistasis, physical capacity-related genes and exceptional longevity: FNDC5 gene interactions with candidate genes FOXOA3 and APOE

dc.contributor.authorFuku N.
dc.contributor.authorDíaz-Peña R.
dc.contributor.authorArai Y.
dc.contributor.authorAbe Y.
dc.contributor.authorZempo H.
dc.contributor.authorNaito H.
dc.contributor.authorMurakami H.
dc.contributor.authorMiyachi M.
dc.contributor.authorSpuch C.
dc.contributor.authorSerra-Rexach J.A.
dc.contributor.authorEmanuele E.
dc.contributor.authorHirose N.
dc.contributor.authorLucia A.
dc.date.accessioned2020-09-02T22:18:04Z
dc.date.available2020-09-02T22:18:04Z
dc.date.issued2017
dc.identifier10.1186/s12864-017-4194-4
dc.identifier.citation18, , -
dc.identifier.issn14712164
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4547
dc.descriptionBackground: Forkhead box O3A (FOXOA3) and apolipoprotein E (APOE) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of 'modifier genes', may contribute to explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population. A total of 1565 individuals were studied, subdivided into 822 middle-aged controls and 743 centenarians. Results: We found a FOXOA3 rs2802292 T-allele-dependent association of fibronectin type III domain-containing 5 (FDNC5) rs16835198 with EL: the frequency of carriers of the FOXOA3 rs2802292 T-allele among individuals with the rs16835198 GG genotype was significantly higher in cases than in controls (P<0.05). On the other hand, among non-carriers of the APOE 'risk' ε4-allele, the frequency of the FDNC5 rs16835198 G-allele was higher in cases than in controls (48.4% vs. 43.6%, P<0.05). Among carriers of the 'non-risk' APOE ε2-allele, the frequency of the rs16835198 G-allele was higher in cases than in controls (49% vs. 37.3%, P<0.05). Conclusions: The association of FDNC5 rs16835198 with EL seems to depend on the presence of the FOXOA3 rs2802292 T-allele and we report a novel association between FNDC5 rs16835198 stratified by the presence of the APOE ε2/ε4-allele and EL. More research on 'gene*gene' and 'gene*environment' effects is needed in the field of EL. © 2017 The Author(s).
dc.language.isoen
dc.publisherBioMed Central Ltd.
dc.subjectAgeing
dc.subjectAPOE
dc.subjectCentenarians
dc.subjectExceptional longevity
dc.subjectFNDC5
dc.subjectFOXO3A
dc.subjectapolipoprotein E
dc.subjectcomplementary RNA
dc.subjectcyclin dependent kinase inhibitor 2B
dc.subjectfibronectin
dc.subjectfibronectin type III domain containing 5
dc.subjectglutathione peroxidase 1
dc.subjectmanganese superoxide dismutase
dc.subjectunclassified drug
dc.subjectapolipoprotein E
dc.subjectfibronectin
dc.subjectFNDC5 protein, human
dc.subjectFOXO3 protein, human
dc.subjecttranscription factor FKHRL1
dc.subjectACTN3 gene
dc.subjectaged
dc.subjectAPOE gene
dc.subjectArticle
dc.subjectASCL1 gene
dc.subjectCDKN2B AS1 gene
dc.subjectcontrolled study
dc.subjectenergy metabolism
dc.subjectepistasis
dc.subjectexceptional longevity
dc.subjectfemale
dc.subjectFNDC5 gene
dc.subjectFOXOA3 gene
dc.subjectgene
dc.subjectgene frequency
dc.subjectgene interaction
dc.subjectgenetic association
dc.subjectgenetic polymorphism
dc.subjectgenotype
dc.subjectGPX1 gene
dc.subjecthuman
dc.subjectJapanese (people)
dc.subjectlongevity
dc.subjectmale
dc.subjectphysical capacity
dc.subjectPTK2 gene
dc.subjectSOD2 gene
dc.subjectTRHR gene
dc.subjectvery elderly
dc.subjectadult
dc.subjectexercise
dc.subjectgenetics
dc.subjectlongevity
dc.subjectmiddle aged
dc.subjectsingle nucleotide polymorphism
dc.subjectyoung adult
dc.subjectAdult
dc.subjectApolipoproteins E
dc.subjectEpistasis, Genetic
dc.subjectExercise
dc.subjectFemale
dc.subjectFibronectins
dc.subjectForkhead Box Protein O3
dc.subjectGene Frequency
dc.subjectGenotype
dc.subjectHumans
dc.subjectLongevity
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectPolymorphism, Single Nucleotide
dc.subjectYoung Adult
dc.titleEpistasis, physical capacity-related genes and exceptional longevity: FNDC5 gene interactions with candidate genes FOXOA3 and APOE
dc.typeArticle


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