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The substitution of tryptophan (Trp) by arginine (Arg) at position 64 in the 3-adrenoceptor ( 3-AR) gene has been associated with obesity, 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 hypertension in the Arab population. All participating subjects were genotyped for this polymorphism using the polymerase chain reaction followed by enzymatic digestion and sequencing. In the angiographed normal control subjects (n 495), 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 (n 981). There was no statistical difference in the distribution 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 variables 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. However, in the presence of other CAD risk factors, this polymorphism may be used as a predictor of CAD.