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Aim Cardiovascular disease (CVD) is a major cause of morbidity and mortality in developed countries. This study aimed to confirm the effect of common putative CVD-associated gene variants ( FTO rs17817449, KIF6 rs20455, 9p21 rs10757274 and 2q36.3 rs2943634) on CVD manifestation, and determine whether this effect differs between younger (< 50 years) and older CVD patients. Methods 1191 controls and 1889 MI patients were analyzed. All participants were Caucasian Czech males aged < 65 years (532 were < 50 years) who were examined at cardiology clinics in Prague, Czech Republic. Variants of FTO , 9p21 , 2q36.3 , and KIF-6 were genotyped using PCR-RFLP or TaqMan assay. Results Variants of FTO (OR 1.48; 95% CI, 1.19–1.84 in a TT vs. GG comparison, p = 0.0005); 9p21 (OR 1.74; 95% CI, 1.41–2.14 in an AA vs. GG comparison, p = 0.0001); and 2q36.3 (OR 1.34; 95%CI, 1.09–1.65 in an AA vs. + C comparison, p = 0.006) were significantly associated with MI in the male Czech population. In contrast, genotype frequencies of KIF-6 (rs20455) were the same in patients and controls (P = 1.00). Nearly identical results were observed when a subset of young MI patients (N = 532, aged < 50 years) was analyzed. Conclusion We confirmed the importance of determining FTO , 9p21 , and 2q36.3 variants as part of the genetic determination of MI risk in the Czech male population. [ABSTRACT FROM AUTHOR]