Cigarette smoking, carrier state of A or G allele of 46A>G and 79C>G polymorphisms of beta2-adrenergic receptor gene, and the risk of coronary artery disease.
BACKGROUND
Coronary artery disease (CAD) is a multifactorial disorder which results from the interactions between a number of genetic and non-genetic factors. Beta-adrenergic receptors are cell-surface receptors which activate adenylyl cyclase by coupling to G proteins. The 46A>G and 79C>G polymorphisms of the beta2-adrenergic receptor gene (ADRB2) have been associated with altered response to sympathetic stimulation.


OBJECTIVE
To assess the relationship between 46A>G and 79C>G polymorphisms of the ADRB2 gene and CAD as well as the associations between these polymorphic variants and traditional risk factors, e.g. cigarette smoking, hypercholesterolaemia, hypertension and overweight or obesity, in determining the risk of CAD.


METHODS
The study population consisted of 207 individuals (white Polish Caucasians aged 20-55 years): 98 patients with angiographically documented CAD (with more than 50% diameter stenosis of at least one of the major coronary vessels) and 109 blood donors with no signs of CAD. The analysis of genetic polymorphisms was performed by means of PCR-RFLP.


RESULTS
The genotype frequencies of both analysed genes in the studied groups were compatible with Hardy-Weinberg equilibrium. We observed higher frequency of the 46A allele in CAD patients than in controls. We also found a tendency to higher prevalence of 46A allele carriers (subjects with genotypes AA+AG) in the CAD group compared to the control group. We did not find any differences in the distribution of genotypes and alleles of 79C>G polymorphism between patients and controls. Multivariate analysis showed that smoking and overweight were independent risk factors of CAD in patients. We found a synergistic effect between carrier state of the 46A allele or 79G allele and smoking, which influences the CAD risk. The 46A allele carriers who smoke as well as carriers of the 79G allele who smoke were much more frequent in the CAD group than in controls. The incidence of 46A allele carriers with hypercholesterolaemia is also higher in patients than in the blood donor group.


CONCLUSIONS
Obtained results indicate a synergistic effect between cigarette smoking and carrier state of 46A allele or 79G allele of ADRB2 in determining the risk of CAD.
Zak
Iwnoa
I
Department of Biochemistry and Medical Genetics, Medical University of Silesia, Katowice, Poland. izak@slam.katowice.pl
Sarecka-Hujar
Beata
B
Krauze
Jolanta
J
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D023921:Coronary Stenosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006937:Hypercholesterolemia; D006973:Hypertension; D008297:Male; D008875:Middle Aged; D009765:Obesity; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2