Objective CD14 is the receptor for lipopolysaccharides and heat shock protein, and C(-260)T polymorphism of CD14 was suggested to be associated with increased risk of coronary artery disease (CAD). We investigated whether the relative significance of chronic infection and autoimmune processes as risk factors of CAD is different according to the CD14 genotype of host. Methods CD14 genotype was determined by polymerase chain reaction in 48 patients with angiographically proven CAD and stable angina pectoris, and in 41 controls without evidence of CAD. Seropositivity to Helicobacter pylori and Chlamydia peumoniae, and antiobody titers to the potential autoantigen human heat shock protein 60 (hHSP60) were measured by enzyme-linked immunosorbent assay. Results Genotype distribution was 31 TT (35%), 43 CT (48%), and 15 CC (17%) and allele and genotype frequencies did not show a significant departure from the Hardy-Weinberg equilibrium. TT genotype was not significantly associated with increased risk of CAD (38% in CAD patients and 32% in controls, p>0.05). Seropositivity to H pylori or C pneumoniae was similar in CAD patients and controls (73% vs. 83%, p>0.05 and 83% vs. 83%, p>0.05, respectively). Antibody titers to hHSP60 were not significantly different between CAD patients and controls (17.4짹5.7 ng/ml vs. 15.9짹5.7 ng/ml, p>0.05). We performed further analysis after dividing patients according to the CD14 genotype. In subjects with TT genotype, seropositivity to H pylori was significantly associated with the presence of CAD (94% in CAD group and 62% in controls, p=0.03). However, in subjects with CT or CC genotypes, seropositivity to H pylori was similar in CAD patients and controls (77% vs. 79%, p>0.05). Seropositivity to C pneumoniae and antibody titers to hHSP60 showed no difference according to the CD14 genotype. Conclusions Seropositivity to H pylori is more important in patients with CD14 TT genotype than non-TT genotypes as a risk factor of CAD. With regard to the risk of CAD, the genetic background may determine the degree of host response and susceptibility to infectious organism.