The peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) is a novel transcriptional co-activator that holds an important role in lipid and glucose metabolism. PGC-1α is a candidate gene for the metabolic syndrome (MS) as well as type 2 diabetes. Recent studies suggested linkage between the chromosomal region of PGC-1α and fasting serum insulin levels, and associates a Gly482Ser polymorphism of the gene with type 2 diabetes and hypertension. In this study, we investigated whether the Gly482Ser variant is associated with the MS per se or other phenotypic traits related to this syndrome. The variant was examined, using PCR-RFLP, in the DanMONICA cohort comprising a population-based sample of 2349 subjects. MS was defined using the National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATPIII) criteria. The allelic frequency of the Ser482 allele was 35.8% in the MS group and 35.6% in the non-MS group (P = 0.74). There were no significant differences across the three groups of genotypes with respect to any of the examined variables, including BMI, waist, fasting serum lipids, plasma glucose, serum insulin, HOMA estimates of insulin resistance and insulin secretion, 24-ambulatory blood pressure or left ventricular mass index. In conclusion, the Gly482Ser polymorphism of the PGC-1α gene is not associated with the metabolic syndrome, related quantitative traits or cardiac hypertrophy among Danish Caucasian subjects.