There has been a considerable increase in the number of studies reporting associations between DNA sequence variation in specific genes and metabolic syndrome (MetS). A low level of cardiorespiratory fitness is also a strong determining factor in the development of MetS. This cross-sectional study was performed to investigate the influence of the interaction between obesity genes and cardiorespiratory fitness on the risk of MetS. Healthy Japanese men (n = 287) participated in this study. All subjects were divided into four groups, fitness level (high and low fitness groups), and age (younger, age < 40 years and middle-aged/older, age ≥ 40 years). The peroxisome proliferator-activated receptor gamma 2 (PPARγ2), the uncoupling protein-2 (UCP2), and the fatty acid binding protein 2 (FABP2) genotypes were analyzed by using real-time polymerase chain reaction (PCR) with Taq-Man probes. Two-way analysis of covariance (ANCOVA) with adjustment for age as a covariate indicated that fitness, the CC genotype of C1431T in the PPARγ2, and the ValVal genotype of Ala55Val in the UCP2 genes interacted to produce a significant effect on MetS risk in Japanese adult men. We concluded that the CC genotype of C1431T in the PPARγ2 and the ValVal genotype of Ala55Val in the UCP2 genes together with low cardiorespiratory fitness may increase the risk of MetS in younger men (age < 40 years), even with adjustment for age.
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