Screening for variants of the uncoupling protein 2 gene in Japanese patients with non-insulin-dependent diabetes mellitus.

We examined genetic mutations in the coding regions of the uncoupling protein 2 (UCP2) gene in 100 patients with non-insulin-dependent diabetes mellitus (NIDDM). The sequences of each exon-intron boundary were detected by polymerase chain reaction (PCR) using specific primer pairs designed in the cDNA sequence of UCP2 and a cycle-sequence method. Using the specific primer pairs in the intron 5'- or 3'-untranslated region, each exon with its exon-intron boundaries was amplified with the PCR method, and the PCR products were analyzed using a single-strand conformation polymorphism (SSCP) method. One nucleotide substitution in exon 4 was found, which exchanged Ala (gcc) at position 55 of the amino acid sequence for Val (gtc), previously reported in Denmark by Urhammer et al in 1997. The polymorphism was reanalyzed in all patients and 120 normal subjects using a PCR-restriction fragment length polymorphism method. There was no difference in the genotype distribution between patients and normal subjects, and our genotype distribution was similar to the Danish study. Furthermore, there were no clinical differences between genotype groups among the patients. No other mutation including the exon-intron boundary was found in these patients. Genetic mutations of UCP2 may not be commonly associated with obesity or diabetes in Japanese subjects.