Several lines of evidence supported the involvement of ECE-1 in the development of atherosclerosis disease. We investigated the C-338A polymorphism of the ECE-1b gene in carotid atherosclerosis. A cohort of 518 Chinese carotid atherosclerosis patients and 518 controls matched by age and sex were examined for the ECE-1b C-338A polymorphism. The ECE-1b-338 A allele was significantly frequent in carotid atherosclerosis patients than in controls (chi(2)=9.167; P=0.002). A alleles had a 26% increased risk of carotid atherosclerosis compared with C alleles (OR=1.26; 95% CI=1.05-1.52). In stratified analyses, the A allele carrying genotypes was significantly associated with an increased risk of carotid atherosclerosis in females (adjusted OR=1.57; 95% CI=1.14-2.23) and a subject with age >or=64 years (adjusted OR=1.72; 95% CI=1.23-1.41). Our results suggested that ECE-1b-338 A allele carrying genotypes might be associated with increased risk of carotid atherosclerosis in the Chinese population.