Vera Mevissen

The interleukin-6 promoter polymorphism is associated with elevated leukocyte, lymphocyte, and monocyte counts and reduced physical fitness in young healthy smokers.

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.

Variants of the CYP11B2 gene predict response to therapy with candesartan

In a prospective trial, patients with an elevated diastolic blood pressure (above 95 mm Hg) received high-dose (16 mg) or low-dose (8 mg) candesartan in addition to standardised medication. A positive response to treatment was defined as a diastolic blood pressure <85 mm Hg at follow-up. Genotyping for two candidate genes was performed in 116 patients. Genotypes of the CYP11B2 promotor polymorphism significantly predicted a positive response to treatment (CC: 67%; TC: 34%; TT: 21%; p=0.005).

Quantification of aortic valve calcification using multislice spiral computed tomography : Comparison with atomic absorption spectroscopy

Objectives:Multislice spiral computed tomography (MSCT) allows the in vivo detection of valvular calcification. The aim of this study was to validate the quantification of aortic valve calcification (AVC) by MSCT with in vitro measurements by atomic absorption spectroscopy. Methods:In 18 patients with severe aortic stenosis, 16 detector row MSCT (SOMATOM Sensation 16, Siemens, Forchheim, Germany with scan parameters as follows: 420 milliseconds tube rotation time, 12 × 0.75 mm collimation, tube voltage 120 KV) was performed before aortic valve replacement. Images were reconstructed at 60% of the RR interval with an effective slice thickness of 3 mm and a reconstruction increment of 2 mm. AVC was assessed using Agatston AVC score, mass AVC score, and volumetric AVC score. After valve replacement, the calcium content of the excised human stenotic aortic valves was determined in vitro using atomic absorption spectroscopy. Results:The mean Agatston AVC score was 3842 ± 1790, the mean volumetric AVC score was 3061 ± 1406, and mass AVC score was 888 ± 492 as quantified by MSCT. Atomic absorption spectroscopy showed a mean true calcification mass (Ca5(PO4)3OH) of 19 ± 8 mass%. There was a significant correlation between in vivo AVC scores determined by MSCT and in vitro mean true calcification mass (r = 0.74, P = 0.0004 for mass AVC score, r = 0.79, P = 0.0001 for volumetric AVC score and r = 0.80, P = 0.0001 for Agatston AVC score) determined by atomic absorption spectroscopy. Linear regression analysis showed a significant association between the degree of hydroxyapatite (given in mass%) in the aortic valve and the degree of AVC (R = 0.74, F = 19.6, P = 0.0004 for mass AVC score, R = 0.80, F = 29.3, P = 0.0001 for Agatston AVC score and R = 0.79, F = 27.3, P = 0.0001 for volumetric AVC score) assessed by MSCT. Conclusion:MSCT allows accurate in vivo quantification of aortic valve calcifications.

APOE alleles are not associated with calcific aortic stenosis

Objectives: To analyse the association of APOE alleles with aortic stenosis (AS) in a large study population. Methods: Patients with AS (n  =  538) and a control group of the same age without heart disease (n  =  536) were recruited. Left heart catheterisation was performed and mean gradient, aortic valve area, presence of stenotic coronary artery disease (CAD) and cardiovascular risk factors (hypercholesterolaemia, hypertension, smoking, diabetes mellitus and family history of CAD) were assessed. The frequency of the APOE major alleles e2, e3 and e4 was assessed by genotyping the polymorphisms APOE334 and APOE472 with a 5′ exonuclease assay (TaqMan). Results: Mean gradient across the aortic valve in cases was 50 (SD 20) mm Hg corresponding to a mean aortic valve area of 0.84 (SD 0.34) cm2. 270 patients with AS had stenotic CAD. Among patients with AS, the prevalence of hypercholesterolaemia (64% v 40%, p < 0.001), smoking (43% v 27%, p < 0.001), diabetes (27% v 17%, p < 0.01), family history of CAD (30% v 21%, p ⩽ 0.05), and male sex (65% v 44%, p < 0.001) was higher in those with than in those without CAD. The frequency of the major alleles was not different between cases and controls (APOE e2: 104 (19.3%) v 94 (17.5%); APOE e3: 319 (59.3%) v 332 (61.9%); APOE e4: 115 (21.3%) v 110 (20.5%); all p > 0.10). Conclusion: APOE e4 is not associated with AS, reflecting the different genetic backgrounds of CAD and AS.

Relationship of Five Inflammatory Gene Polymorphisms with Morbidity and Mortality in 533 Patients Admitted to an ICU

BackgroundThe aim of this study was to analyze the association of polymorphisms of five candidate genes with the outcome of consecutive patients admitted to a medical ICU.Materials and MethodsThe study population was prospectively recruited. Inclusion criteria were admission to the ICU and written informed consent by the patients or their relatives. A total of 533 patients were recruited. The morbidity was assessed by SAPS II Score. Outcome data of in hospital mortality and length of ICU and hospital stay were obtained. Genotyping for genetic polymorphisms (CRP 1059, IL1B −511, CTGF −477, CCR2 64VI, IL6 −174) were performed by allele-specific fluorogenic oligonucleotide probes (TaqMan analysis).ResultsAll of the investigated polymorphisms were not associated with an altered outcome. There was no difference in morbidity and ICU or in-hospital mortality (neither in cross tabs analysis nor in Kaplan Meier or Cox regression analysis including age, gender and diagnosis as covariates) between the different genotypes.ConclusionsGenotyping of the investigated polymorphism for risk stratification of patients admitted to ICU does not seem to be appropriated.