Lectin-like oxidized low-density lipoprotein receptor (LOX-1/OLR1) has been suggested to play a role in the progression of atherogenesis. We analyzed the OLR1 gene and found a single nucleotide polymorphisin (SNP), G501C, in patients with ischemic heart disease from a single family, which resulted in the missense mutation of K167N in LOX-1 protein. We compared the group of patients with myocardial infarction (MI) (n = 102) with a group of clinically healthy subjects (n = 102), and found that the MI group had a significantly high frequency of 501G/C + 501C/C (38.2%) compared with the healthy group (17.6%; p < 0.002). The odds ratio for the risk of MI associated with the 501G/C + 501C/C genotype was 2.89 (95% CI, 1.51-5.53). These findings suggest that OLR1 or a neighboring gene linked with G501C SNP is important for the incidence of MI. Manipulating LOX-1 activity might be a useful therapeutic and preventative approach for coronary artery disease, especially for individuals with the G501C genotype of OLR1. (C) 2003 Elsevier Science (USA). All rights reserved.