Inflammation is associated with atherosclerosis of coronary arteries. Chemokines have an important role in inflammation. The CCR2 chemokine receptor mediates leukocyte chemoattraction, which is involved in the pathogenesis of coronary heart disease. We prospectively studied 1960 consecutive patients aged under 65 years and referred for a first-time left ventricular catheter. Left heart catheters were analyzed by two independent cardiologists for the presence of myocardial infarction (regional wall motion abnormality) and moderate or severely reduced left ventricular function on cineventriculography and presence of coronary atherosclerosis on angiography. Genotyping for CCR2 V64I polymorphism was performed. The presence of the rare allele of the CCR2 gene was significantly associated with a higher prevalence of myocardial infarction on cinventriculography (32.0% vs. 24.2%, moderately or severely reduced left ventricular function (14.0% vs. 9.5%) and NYHA class III or IV (16.7% vs. 12.2%). The association of the CCR2 genotype with heart failure was not independent of the presence of myocardial infarction in multivariate analysis. There was no association of the CCR2 genotype with coronary atherosclerosis. The CCR2 genotype seems to predispose patients for myocardial infarction before the age of 65 years. The higher prevalence of heart failure in gene carriers with the rare alle might be a consequence of myocardial infarction. If the CCR2 genotype is associated with higher mortality in the general population must be investigated in further studies.
Smoking and interleukin-6 are important factors in driving inflammation. This study assessed the relationship between smoking, interleukin-6 genotype, physical fitness, and peripheral blood count in healthy young men. For this interleukin-6 promoter polymorphism -174 genotype-phenotype association study 1,929 healthy German male aviators recruited at the central German Air Force Institute of Aviation Medicine were stratified by smoking habits. Cardiovascular fitness was expressed as maximal physical working capacity (PWCmax) in watts per kilogram body weight as assessed by maximal exercise testing by cycle ergometry up to physical exhaustion. Smokers had higher leukocyte and lymphocyte counts than nonsmokers and lower PWCmax. In the overall study population the C allele of the interleukin-6 polymorphism was weakly associated with elevated leukocytes and lymphocytes; in nonsmokers the interleukin-6 polymorphism was not associated with altered phenotypes, but in smokers the interleukin-6 C allele was associated with higher leukocytes, lymphocytes, and monocytes and with lower PWCmax. Smoking is thus associated with elevated leukocytes and lymphocytes and with reduced physical fitness. Gene carriers with the interleukin-6 C allele may suffer particularly from cigarette smoking.
The aim of this study was to assess the association of the angiotensinogen M235T polymorphism with arterial blood pressure (BP) at rest and under physical stress in a homogeneous large-scale study population. In all, 1903 men who passed routine medical examination for military flying duty were recruited. BP and heart rate were measured at rest, during, and after bicycle ergometry. Genotyping for the AGT M235T polymorphism was carried out by PCR and RFLP technique. The AGT T235 allele was associated with a significantly higher diastolic BP (n ¼ 1903; MM 81 7 8, MT 83 7 7, TT 83 7 8; P ¼ 0.003). Pulse pressure (PP) at rest differed significantly between AGT genotypes (n ¼ 1903; MM 51 7 10 mmHg, MT 49 7 10 mmHg, TT 49 7 10 mmHg; P ¼ 0.001). During physical activity, BP values showed no significant difference between genotypes. In healthy young men, the AGT T235 allele is significantly associated with elevated diastolic BP but also reduced PP at rest. During physical activity, the AGT polymorphism had no impact on blood pressure, indicating the existence of other counteracting mechanisms, which might balance the influence of this gene.
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