The uncoupling protein (UCP) 2 gene is expressed in adipose tissues and skeletal muscles, which are important sites for variations in energy expenditure. The objective of the current study was to examine the potential impact of a C-->T substitution in exon 4, resulting in an alanine to valine substitution at codon 55, on the Metabolic Syndrome in 284 unrelated Swedish men born in 1944. The subjects were genotyped using PCR amplification of the exon 4 region of the UCP2 gene followed by digestion with the restriction enzyme EclHK1. The allelic frequencies were 0.56 for allele Ala and 0.44 for allele Val. No association was found between the Ala55Val SNP and obesity and blood levels of insulin, glucose, and lipids as well as blood pressure and circulating hormones. From these data, we conclude that the C-->T substitution in exon 4 of the UCP2 gene does not contribute to the predisposition to be affected by the Metabolic Syndrome.