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

BMC Genomics

Research

Enzo Emanuele¹  Yukiko Abe²  Yasumichi Arai²  José A. Serra-Rexach³  Haruka Murakami⁴  Motohiko Miyachi⁴  Alejandro Lucia⁵  Noriyuki Fuku⁶  Nobuyoshi Hirose⁶  Hisashi Naito⁶  Hirofumi Zempo⁶  Roberto Díaz-Peña⁷  Carlos Spuch⁸ 

[1] 2E Science, Robbio, (PV), Italy;Center for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan;Centro de investigación biomédica en Envejecimiento y Fragilidad (CIBERFES), Madrid, Spain;Department of Physical Activity Research; National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan;European University and Research Institute i+12, Madrid, Spain;Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan;Hospital Universitari Institut Pere Mata, IISPV, URV. CIBERSAM, Reus, Spain;Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile;Neurology Group, Galicia Sur Health Research Institute (IIS Galicia Sur), Centro de investigación biomédica en red del área de salud mental (CIBERSAM), Vigo, Spain;

关键词: Exceptional longevity;    Centenarians;    FOXO3A;    FNDC5;    APOE;    Ageing;   

DOI  :  10.1186/s12864-017-4194-4

来源: Springer

【 摘 要 】

BackgroundForkhead 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.ResultsWe 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).ConclusionsThe 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.

【 授权许可】

CC BY   
© The Author(s). 2017