Metabolic syndrome (MS) is a clinical feature, closely associated with insulin resistance, one of the prime underlying causes of overall cardiovascular morbidity, including coronary heart disease (CHD). Considering the association between PC-1 121Q genotype and insulin resistance phenotype, the aim of the present study was to investigate the contribution of PC-1 K121Q polymorphism to the development of MS and its concomitant disorders in CHD patients.A total of 130 Caucasians from Serbia, including 80 CHD patients (aged 59.4+/-8.6 years, of a mean BMI 28.9+/-3.9 kg/m2) and 50 control subjects (aged 48.0+/-6.4 years, of a mean BMI 29.6+/-2.1 kg/m2), were genotyped for PC-1 K121Q using a mutagenic separated PCR assay, in order to determine the prevalence of the PC 121Q variant in individuals suffering from CHD and its association with MS.The frequency of PC-1 121Q allele found in CHD patients was 28.5%, with significantly (P<0.01) higher prevalence in those with MS (40% vs. 10%). Both MS (P<0.01) and its components [central obesity (P<0.01), low HDL-cholesterol (P<0.01) and high triglycerides (P<0.05)] were significantly more prevalent in CHD 121Q carriers compared to CHD patients who exhibited the wild-type genotype. A binary logistic regression model has revealed that PC-1 121Q allele carriers had a 5.5 fold increased odds (95%CI: 1.4-20.9, P=0.01) for the MS compared to wild-type carriers. The PC-1 121Q allele contributed to MS components as well, although these associations did not reach statistical significance.The findings of the present study support the hypothesis that the PC-1 (ENPP1) 121Q allele is associated with the genetic susceptibility for MS in patients with CHD. Further studies and more extensive research in this area are needed, not only to confirm this association, but to elucidate it in more details.