A common polymorphism of uncoupling protein 2 gene is associated with hypertension

J Hypertens. 2004 Jan;22(1):97-102. doi: 10.1097/00004872-200401000-00018.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Biomarkers / blood
  • Blood Pressure / genetics
  • Body Mass Index
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Hyperinsulinism / genetics
  • Hypertension / genetics*
  • Insulin / blood
  • Insulin Resistance / genetics
  • Ion Channels
  • Japan
  • Male
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Obesity
  • Polymorphism, Genetic / genetics*
  • Statistics as Topic
  • Systole / genetics
  • Uncoupling Protein 2


  • Biomarkers
  • Insulin
  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • UCP2 protein, human
  • Uncoupling Protein 2