Background-The CD14 receptor of monocytes is an important mediator for the activation of monocytes/macrophages by endotoxins from the envelope of Gram-negative bacteria (lipopolysaccharides). We identified a polymorphism in the CD14 receptor and examined whether this genetic marker influenced the expression of the CD14 receptor on monocytes and affected the predisposition to myocardial infarction. Methods and Results-We identified a C(Ϫ260)3 T nucleotide change, creating a HaeIII polymorphism in the promoter of the CD14 gene. The polymorphism was determined in 178 male patients Ͻ65 years old (cases; average age, 55.9Ϯ6.3 years) at the time of their first myocardial infarction and in 135 representative selected male control subjects (controls; average age, 55.2Ϯ11.5 years). The frequency of the T allele (absence of the cutting site) was 0.49 in cases and 0.35 in controls (Pϭ0.0005; OR, 1.781; 95% CI, 1.286 to 2.465). Subsequently, we measured the expression of monocyte CD14 by flow cytometry in 18 volunteers with different CD14 genotypes. A significantly higher density of the CD14 receptor was shown in the T/T homozygotes than in the others (Pϭ0.0028). Conclusions-A higher frequency of allele T(Ϫ260) in the promoter of the CD14 receptor gene was found in myocardial infarction survivors than in controls. At the same time, this variation was associated with a higher density of CD14 receptors in healthy volunteers. Therefore, we can conclude that in addition to the well-established risk factors, a genetically determined reaction of monocytes/macrophages to infectious stimuli could play an important role in the process of atherosclerosis. (Circulation. 1999;99:3218-3220.)

The importance of an APOAV gene for plasma triglyceride level determination has been shown on transgenic and knockout mice. We examined whether APOAV variants are associated with plasma triglyceride levels and risk of myocardial infarction (MI). We have evaluated the influence of APOAV polymorphisms (T-1131>C and S19>W) on plasma triglycerides in 1191 males and 1368 females representatively selected from the Czech population. Triglycerides have been analysed in 1997 and 2001. Subsequently, we have analysed the genotype frequencies of the APOAV polymorphism in 435 patients with MI. T-1131>C variation in the APOAV gene affects the plasma triglyceride showing a higher level in C-1131 carriers than in T/T-1131 homozygotes. This association has been observed both in males and females (p < 0.001). Similarly, plasma triglycerides were also significantly influenced by the S19>W APOAV genotypes. In both males and females, the W19 carriers have triglycerides significantly (p < 0.001) higher compared to the S19 homozygotes. In a group of MI patients, the frequency of the rare homozygotes for at least one APOAV polymorphism (C/C-1131 and/or W/W19) was significantly higher than that in the population sample (7.4 vs 2.0%, p < 0.00001). We conclude that variations in the APOAV gene not only play a role in genetic determination of triglyceride levels but also could influence risk of MI.

A potential candidate gene that could contribute to the education process is the apolipoprotein E (apo E) gene that has been shown to correlate with memory function and memory decline. We measured apo E polymorphism in groups of probands with different levels of education selected from a population sample. In the group of probands with higher education (n = 82), 24.4% had the e4 allele, compared with 7.3% who had the e2 allele. A reverse association was found in the group that left school aged 15 (n = 36) – 8.3% had the e4 allele and 13.9% had the e2 allele. Eighty-seven percent of the probands with the allele e4 reached higher education, compared to only 54.5% with the allele e2. The difference between the groups is statistically significant (p = 0.039), and this may indicate some role for the apo E polymorphism in subjects` intelligence or ability to learn.

AimsThe Systematic COronary Risk Evaluation (SCORE) scale assesses 10 year risk of fatal atherosclerotic cardiovascular disease (CVD), based on conventional risk factors. The high-risk SCORE version is recommended for Central and Eastern Europe and former Soviet Union (CEE/FSU), but its performance has never been systematically assessed in the region. We evaluated SCORE performance in two sets of population-based CEE/FSU cohorts.Methods and resultsThe cohorts based on the World Health Organization MONitoring of trends and determinants in CArdiovascular disease (MONICA) surveys in the Czech Republic, Poland (Warsaw and Tarnobrzeg), Lithuania (Kaunas), and Russia (Novosibirsk) were followed from the mid-1980s. The Health, Alcohol, and Psychosocial factors in Eastern Europe (HAPIEE) study follows Czech, Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002–05. In Cox regression analyses, the high-risk SCORE ≥5% at baseline significantly predicted CVD mortality in both MONICA [n = 15 027; hazard ratios (HR), 1.7–6.3] and HAPIEE (n = 20 517; HR, 2.6–10.5) samples. While SCORE calibration was good in most MONICA samples (predicted and observed mortality were close), the risk was underestimated in Russia. In HAPIEE, the high-risk SCORE overpredicted the estimated 10 year mortality for Czech and Polish samples and adequately predicted it for Russia. SCORE discrimination was satisfactory in both MONICA and HAPIEE.ConclusionThe high-risk SCORE underestimated the fatal CVD risk in Russian MONICA but performed well in most MONICA samples and Russian HAPIEE. This SCORE version might overestimate the risk in contemporary Czech and Polish populations.

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