Experimental studies have demonstrated KLOTHO gene polymorphism might be associated with vascular atherosclerosis and calcification. However, the impact of this genetic variant on human coronary arteries still remains to be elucidated. We investigated the effect of a KLOTHO gene variant on coronary artery stenosis and calcification. Four hundred and thirty-four patients referred for chest pain were enrolled. All the patients underwent coronary angiography and were investigated for polymorphism of the KLOTHO G395A gene. Coronary artery disease (CAD) was defined as > or = 50% diameter stenosis in at least one coronary artery. The other patients were considered to be controls. Homozygotes or heterozygotes for G395A were significantly more common in the CAD patients than in the controls (30.2% versus 21.5%, P = 0.039). In the subgroup aged < 60 years, the G395A mutant was more frequent in CAD than in control (35.3% versus 18.8%, P = 0.016), but in patients > or = 60 years, there was no difference (28.0% versus 24.1%, P = 0.473). Using multivariate analysis, we identified the KLOTHO gene G395A mutant as an independent risk factor of CAD (OR 1.712, 95% CI [1.066-2.749], P = 0.026). The frequency of the KLOTHO gene G395A mutant was not different between the calcified and noncalcified coronary artery groups (25.7%, 26.4%, respectively, P = 0.861) and an A allele carrier state was not an independent risk factor of coronary artery calcification. In conclusion, the KLOTHO gene G395A allele carrier state may be associated with CAD but not with coronary artery calcification in this Korean population.