Common single nucleotide polymorphisms in the FNDC5 gene are associated with glucose metabolism but do not affect serum irisin levels in Japanese men with low fitness levels

Objective This cross-sectional study analyzed the association of serum irisin concentrations with cardiorespiratory fitness levels and common single nucleotide polymorphisms (SNPs) in the FNDC5 gene and examined the relationships between cardiorespiratory fitness levels, common SNPs in FNDC5, and glucose metabolism. Materials/Methods Cardiorespiratory fitness was assessed by measuring peak oxygen uptake (VO₂peak) and serum irisin levels by ELISA in 163 Japanese men (age, 21-79 years). Subjects were divided into low- and high-fitness groups within each age group according to the median VO ₂peak value. Common SNPs (rs3480 and rs16835198) of the FNDC5 gene were genotyped with the TaqMan assay. Glucose metabolism was evaluated by measuring HbA1c, fasting plasma glucose (FPG), insulin levels, and HOMA-IR. Results Serum irisin levels were negatively correlated with age (p < 0.001) and not associated with the VO₂peak or HOMA-IR. In the low-fitness group, SNP analysis revealed that subjects with the rs3480 AG and GG genotypes had higher levels of insulin and HOMA-IR than those with the AA genotype (p < 0.01; no significant difference was observed in the high-fitness group). The GG genotypes of rs16835198 were associated with increased HbA1c and FPG in the low-fitness group only (p < 0.05). SNPs and both fitness groups were not associated with serum irisin levels. Conclusions In Japanese men, cardiorespiratory fitness levels and common SNPs in FNDC5 are not associated with circulating irisin levels, whereas high cardiorespiratory fitness abolishes the association between the rs3480 and rs16835198 SNPs and glucose metabolism independent of serum irisin levels.