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The mitochondrial uncoupling proteins UCP2 and UCP3 are implicated in energy metabolism and regulation of reactive oxygen species, which are closely involved in autonomic nervous system function. Heart rate variability (HRV) reflects cardiac autonomic regulation and has been used to evaluate dysfunction of the autonomic nervous system in hypertension and cardiovascular diseases. We examined the association between polymorphisms in the UCP2 and UCP3 genes and HRV in healthy young Japanese men.The 45 bp insertion/deletion polymorphism in exon8 of UCP2 and the −55C/T polymorphism in the UCP3 promoter region were genotyped (n = 255). Cardiac autonomic function was evaluated by power spectral analysis of HRV during supine rest and in a standing position. Low-frequency (<0.15 Hz) and high-frequency (>0.15 Hz) components of HRV were quantified by frequency domain analysis.The I/I genotype of the UCP2 45 bp insertion/deletion polymorphism was associated with relatively higher blood pressure and HRV sympathetic indices (low frequency percentage and low frequency:high frequency ratio) at supine rest. For the −55C/T polymorphism of UCP3, individuals carrying the −55T allele had significantly lower HRV sympathetic indices, but higher HRV parasympathetic indices (high frequency and high frequency percentage), than carriers of the C/C genotype at standing. Both UCP2 and UCP3 polymorphisms were significantly associated with a third-degree family history of hypertension, diabetes, and obesity. Additionally, carriers of the UCP2 45 bp I allele −UCP3 −55C/C combined genotype had the lowest HRV sympathetic and the highest HRV parasympathetic indices at standing among the combined genotypes.UCP2 and UCP3 polymorphisms were associated with HRV in young and healthy states, suggesting a significant relationship between autonomic cardiovascular regulation and UCP2/UCP3 polymorphisms.