Association of GNB3 gene with pulse pressure and clustering of risk factors for cardiovascular disease in Japanese

Biochem Biophys Res Commun. 2004 Apr 9;316(3):744-8. doi: 10.1016/j.bbrc.2004.02.113.

Abstract

Heterotrimeric guanine nucleotide-binding proteins (G proteins) mediate many pathways including the beta-adrenergic signaling pathway. The C825T polymorphism in the gene coding for the beta3 subunit of G proteins (GNB3) has been shown to be associated with several phenotypes such as hypertension, obesity, and diabetes mellitus comprising the metabolic syndrome. The GNB3 C825T polymorphism may therefore be associated with many atherosclerosis-related phenotypes. On these grounds, we studied the C825T polymorphism in relation to atherosclerosis-related phenotypes in a large Japanese population. Analyses in general linear models showed that T carriers had a significantly wider pulse pressure (P=0.0089) as well as a significantly higher systolic blood pressure (P=0.026). In contrast, analyses in logistic regression models showed that the C825T polymorphism was not significantly associated with each of the four major classical risk factors for cardiovascular and cerebrovascular disease (obesity, hypertension, hypertriglyceridemia, and diabetes mellitus). However, a significantly higher percentage of subjects had none of the four disorders in CC homozygotes than in T carriers (P=0.026). Thus, the C825T polymorphism was significantly associated with clustering of these four risk factors. Although the effect of the gene on each phenotype appears to be weak, considering the combined impact of the effects of the C825T polymorphism on risk factors, the GNB3 gene may be an important gene for human health.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arteriosclerosis
  • Blood Pressure*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism*
  • Cluster Analysis
  • DNA / chemistry
  • Female
  • Genotype
  • Heterotrimeric GTP-Binding Proteins / chemistry*
  • Heterotrimeric GTP-Binding Proteins / genetics*
  • Homozygote
  • Humans
  • Japan
  • Logistic Models
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic
  • Risk Factors
  • Signal Transduction

Substances

  • G-protein beta3 subunit
  • DNA
  • Heterotrimeric GTP-Binding Proteins