Beta 3 Adrenergic Receptor Trp64Arg Polymorphism and Manifestation of Coronary Artery Disease in Arabs

The substitution of tryptophan (Trp) by arginine (Arg) at posi- tion 64 in the 3-adrenoceptor (3-AR) gene has been associated with obe- sity, diabetes mellitus, and coronary artery disease (CAD). We have investigated whether the Trp64Arg polymorphism is associated with the manifestation of CAD or one of its important risk factors, such as obesity, diabetes mellitus, elevated cholesterol and triglyceride levels, or hyperten- sion in the Arab population. All participating subjects were genotyped for this polymorphism using the polymerase chain reaction followed by enzy- matic digestion and sequencing. In the angiographed normal control subjects (n495), 90.3% were homozygous Trp/Trp, 9.5% were heterozygous Trp/ Arg, and 0.2% were homozygous for the Arg/Arg genotype, compared to 87%, 12.3%, and 0.7%, respectively, among angiographically confirmed CAD patients (n981). There was no statistical difference in the distribu- tion of genotypes or allele frequencies between the CAD and control groups. We carried out a stepwise logistic regression analysis to study the possible combined effect of the genotypes and other risk factors on CAD. All vari- ables were retained in the model, with p values of 0.014, 0.006, 0.005, 0.001, 0.045, 0.002, 0.001, and 0.016 for genotype, diabetes mellitus, sex, family history of CAD, obesity, myocardial infarction, smoking, and age, respectively. In conclusion, the Trp64Arg polymorphism of the 3-AR gene does not represent an independent risk factor for CAD in Arabs. How- ever, in the presence of other CAD risk factors, this polymorphism may be used as a predictor of CAD. The 3-adrenoceptor (3-AR) forms an essential component of the cardiovascu- lar sympathetico-adrenoceptor signaling systems. Human 3-AR is expressed