Objectives: The genes responsible for obesity are also candidate genes for obesity-related conditions, such as hypertension and type 2 diabetes. A functional polymorphism in the uncoupling protein 2 (UCP2) promoter has been reported to be associated with obesity in Caucasians. To clarify the contribution of this polymorphism to obesity and related conditions, we studied the association of the -866 G/A polymorphism of the UCP2 gene with obesity, hypertension and type 2 diabetes mellitus.
Methods: A total of 632 unrelated Japanese subjects were studied: 342 type 2 diabetic patients (among them, 158 patients complicated with hypertension), 156 hypertensive patients without diabetes mellitus and 134 control subjects. The -866 G/A polymorphism of UCP2 was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP).
Results: The frequency of the minor A allele was significantly higher in Japanese than in Caucasians (48.9 versus 37.2%, P=0.01). In contrast to the significant association with obesity in Caucasians, the polymorphism was not associated with obesity in Japanese. The polymorphism, however, was significantly associated with hypertension in Japanese (frequency of A allele: 51.8% in hypertensives versus 46.6% in normotensives, P<0.05). No significant difference was observed in body mass index (BMI), fasting insulin level or HOMA-R between patients with different genotypes.
Conclusion: These data indicate that the polymorphism of the UCP2 gene is associated with hypertension, and suggest the possibility of UCP2 as a target molecule for studies on the etiology and treatment of hypertension.