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Biomedical subjects

G Assmann

Publications and source records attributed to G Assmann.

462 records · Page 26Linked to original sources
PubMedDate not supplied

Extended haplotype analysis reveals an association of TNF polymorphisms with susceptibility to systemic lupus erythematosus beyond HLA-DR3.

OBJECTIVE: To study the relative contribution of tumour necrosis factor (TNF) and HLA-DRB1 polymorphisms to the genetic susceptibility to systemic lupus erythematosus (SLE) via an extended haplotype analysis. METHODS: We performed an association study in 205 unrelated German Caucasian patients with SLE fulfilling the 1997 revised American College of Rheumatology (ACR) criteria. Healthy age-, ethnically- and sex-matched individuals (n = 157) served as controls. HLA-DRB1 typing was performed by a sequence-specific oligonucleotide hybridisation assay. Two TNF single nucleotide polymorphisms (SNPs) and two multiallelic microsatellites were analysed by mutagenically separated polymerase chain reaction (PCR) or fragment length analysis, respectively. Extended haplotypes were reconstructed with the PHASE software. RESULTS: Alleles for all polymorphic loci studied and the most frequent haplotypes showed a significantly different distribution between SLE patients and controls. The alleles HLA-DR2, DR3, TNFd1, TNF2, TNFB*1, and TNFa2, designated as risk alleles, and the extended haplotypes DR3-TNFd1-TNF2-TNFB*1-TNFa2 and DR2-TNFd3-TNF1-TNFB*2-TNFa11 prevailed in SLE patients. TNF risk alleles were strongly positively linked with HLA-DR3 and negatively linked with HLA-DR2. Thus, in HLA-DR3 haplotypes individual effects of TNF polymorphisms could not be resolved. By contrast, HLA-DR2 showed an association with SLE independently of TNF risk alleles, while the risk increased further when they were present. In haplotypes lacking HLA-DR2 and DR3, the alleles TNFdl and TNF2 contributed independently to SLE susceptibility. CONCLUSION: Extended haplotype analysis revealed HLA-DR3 independent associations of TNF polymorphisms with susceptibility to SLE. Haplotypes that have been shown to be associated with different TNF-alpha production capacity may prevail in different disease subgroups.

Adolescent↗
PubMedDate not supplied

Apolipoprotein E polymorphism and coronary artery disease.

Lipid status and apolipoprotein E phenotypes were tested in 1000 patients who underwent coronary angiography. The same number of factory employees was chosen as a control group. We distinguished between six different apolipoprotein E phenotypes and determined their frequencies in all groups. For the three homozygous phenotypes E3/3, E4/4, and E2/2, the percentage distribution in the group of factory employees was 62.7%, 2.3%, and 0.8%, respectively; for the three heterozygous phenotypes E4/3, E3/2, and E4/2, we determined frequencies of 20.3%, 11.0%, and 3.0%, respectively. In the group of patients with and without signs of coronary atherosclerosis, we observed almost the same frequencies except that heterozygotes (E3/2) occurred significantly more frequently in the group of coronary angiography patients unaffected by coronary sclerosis. Cholesterol and triglyceride values were significantly elevated in patients with coronary artery disease, whereas high density lipoprotein cholesterol levels were not significantly different. The data further suggest that apolipoprotein E2/2 homozygosity, despite the presence of beta-very low density lipoproteins in the plasma of these patients, cannot be considered a biochemical indicator of an increased risk of coronary atherosclerosis. On the other hand, apolipoprotein E3/2 heterozygosity may have a protective effect on the development of early atherosclerosis.

Adult↗
PubMedDate not supplied

[Assessment of cardiovascular risk--PROCAM and new algorithms].

The absolute risk for myocardial infarction is best determined using algorithms or point schemes which have been developed on the basis of large prospective, epidemiological studies. In Germany, for instance, the PROCAM score developed in Münster is leading in this field. The role of new risk factors lies in the optimum risk prediction in patients with intermediary or high risk for myocardial infarction. It is not necessary to determine additional risk factors in low-risk-patients. At present there is however no conclusive epidemiological evidence so that the decision for investigating newer risk factors lies with the physician in charge. So far the target level for LDL cholesterol in patients with intermediate risk was set at 130 mg/dL, whereas in high risk patients LDL cholesterol should not be more than 100 mg/dL. The results of newer studies suggest that it might be appropriate to define a new category of patients with very high risk in whom the LDL cholesterol value should not exceed 70 mg/dL. This inference must however be substantiated by further studies before it becomes part of the general recommendations for treatment.

Algorithms↗
PubMedDate not supplied

Dietary habits in Eastern Germany: changes after reunification and their relation to CHD risk profiles (DRECAN).

As part of the DREsden CArdiovascular risk and Nutrition study, 2038 participants, selected from a cohort of 3076 workers in the Dresden area, underwent a detailed nutritional analysis of the periods before and after German reunification. Although protein, fat, carbohydrate, and total calorie intake did not change in Dresden after reunification, polyunsaturated fat replaced 17% of the saturated fatty acids, dairy product intake tripled, and fruit intake increased by 70%. Relative to a reference PROCAM 'western' cohort, the 90th percentile of triglycerides was higher in middle-aged men, and the levels of total cholesterol and HDLC were higher in all males. Serum LDLC levels in males and females were similar. Serum lipid concentrations and the prevalence of hyperlipidemia were similar to those of the PROCAM cohort, but smoking was less common. In young males and females, body mass index was higher; hypertension was more frequent. We assume that the differences in nutrition and risk profile before reunification were less substantial than commonly believed.

Adult↗
PubMedDate not supplied

The biologic lower detection limit of six ultrasensitive PSA assays.

BACKGROUND: The benefit of monitoring patients with prostate cancer (PCA) by ultrasensitive measurement of prostate specific antigen (PSA) is frequently discussed. Usually, the analytic lower detection limit of an ultrasensitive assay is determined by the manufacturer. As the analytic lower detection limit does not take into account interfering factors of human serum, the biologic lower detection limit, which is defined as PSA concentration detected in PSA-free human serum, plus 3 standard deviations, is of greater interest. MATERIALS AND METHODS: We investigated the biologic lower detection limit of six ultrasensitive PSA assays. Sera from 15 men with bladder cancer after radical cystoprostatectomy and from 30 healthy women were applied. Hence, we expected no PSA of prostatic origin. RESULTS: The biologic lower detection limit obtained using these sera was up to 30 fold higher (men, 0.29-0.63 ng/ml; women, 0.03-0.69 ng/ml) than the analytic lower detection limit (0.01-0.09 ng/ml). CONCLUSIONS: PSA measurement in sera obtained from men without prostate and women results in PSA values above the ultrasensitive range. Therefore, advantages provided by ultrasensitive PSA measurement in monitoring PCA patients after radical prostatectomy are limited.

Environmental Monitoring↗