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Introduction: Genetic susceptibility affects atherosclerosis in humans. Polymorphisms of genes of angiotensin-converting enzyme (ACE), lipoprotein APOE (APOE), IL1 receptor antagonist (IL1Ra) and myeloperoxidase (MPO) are associated with several components of atherosclerotic disease. We evaluated allelic and genotypic frequencies and their association with age at presentation, vascular risk factors, and presence of symptoms in subjects with carotid atherosclerosis.Methods: We studied Argentine patients with severe carotid atherosclerosis and controls from the general population. Age, vascular risk factors and presence of neurological symptoms were recorded. DNA was obtained from peripheral blood and PCR or PCR-RFLP were used to typify ACE, APOE, IL1Ra, and MPO genes. Allelic and genotypic frequencies were compared and genotypic susceptibility variants were established. Chi-square and good fit test were applied for differences between expected and observed frequencies.Results: There were 137 patients, 36 women and 101 men, aged 67±8 years. Symptomatic subjects younger than 60 years had higher frequency of the alleles ACE-DD, associated to vasoconstriction, endothelial proliferation, oxidation, and apoptosis (p<0.01); IL1RN-12/22, associated to inflammation and apoptosis (p<0.01); and MPO*GA/AA, associated to less oxidative response and proatherogenic (p<0.05). Subjects older than 60 years had a genetic profile similar to the general population without atherosclerosis, with similar prevalence of ACE-ID/II, IL1RN-11, and MPO-GG and a higher frequency of APOE23, 24 and 34m. Independent associations of ACE*D and IL1RN*2 with dyslipidemia and of MPO-GA and APOE-34 with hypertension were observed.Conclusions: Subjects with carotid atherosclerosis are genetically different from the general population. Carriers of certain gene variants were predominant among atherosclerotic subjects, suggesting susceptibility, and others were more prevalent in controls, suggesting protection. Some polymorphisms and their combinations are associated with occurrence of symptomatic disease at an earlier age. The genetic profile of older patients does not substantially differ from the general population.