Genetic and immunological risk factors and carotid artery atherosclerosis

Abstract Atherosclerosis is a multifactorial disease with numerous genes and environmental factors affecting its intiation and progression. During the past years many candidate genes for atherosclerosis have been suggested, and it has also become evident that the immune system plays a part in atherogenesis. Early atherosclerotic changes can be effectively detected by measuring carotid artery intima-media thickness (IMT). In the present study the associations between IMT and polymorphisms of three candidate genes for atherosclerosis were studied: endothelial nitric oxide synthase (eNOS), apolipoprotein E (apoE) and paraoxonase-1 (PON1). To assess the role of immunological factors determining carotid atherosclerosis, CRP and circulating autoantibodies to oxidised LDL were studied in relation to IMT. The study population consisted of 519 hypertensive and 526 control subjects from a middle-aged population in Oulu, Finland. The results showed that the investigated polymorphisms of eNOS and PON1 genes were not associated with IMT, suggesting that these polymorphisms are not major risk factors for atherosclerosis in the general Caucasian population. A significant interaction between the apoE polymorphism and smoking in relation to IMT was observed among men, indicating that carriers of the ε4 allele may be particularly prone to the atherogenic effects of smoking. This interaction was especially clear in hypertensive subjects. CRP was strongly associated with IMT before adjusting for confounding factors. After the adjustment, this association diasppeared. The finding suggests that instead of early atherosclerosis CRP may be related to the later phases of the disease. This may partly explain the strong correlation between CRP and future cardiovascular events. IgM type of autoantibodies binding to oxidised LDL were inversely associated with IMT, and this finding remained after adjusting for previously known risk factors for atherosclerosis, implying a possible protective role for these antibodies in atherogenesis