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Biomedical subjects

Berthold Hoppe

Publications and source records attributed to Berthold Hoppe.

7 recordsLinked to original sources
PubMed2006

Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case-control study.

Peptidylarginine deiminase type 4 (PADI4) genotypes were shown to influence susceptibility to rheumatoid arthritis (RA) in the Japanese population. Such an association could not previously be confirmed in different European populations. In the present study, we analysed exons 2-4 of PADI4 in 102 German RA patients and 102 healthy individuals to study the influence of PADI4 variability on RA susceptibility by means of haplotype-specific DNA sequencing. Analyses of the influence of PADI4 and HLA-DRB1 genotypes on disease activity and on levels of anti-cyclic citrullinated peptide antibodies were performed. Comparing the frequencies of PADI4 haplotype 4 (padi4_89*G, padi4_90*T, padi4_92*G, padi4_94*T, padi4_104*C, padi4_95*G, padi4_96*T) (patients, 14.7%; controls, 7.8%; odds ratio = 2.0, 95% confidence interval = 1.1-3.8) and carriers of this haplotype (patients, 27.5%; controls, 13.7%; odds ratio = 2.4, 95% confidence interval = 1.2-4.8), a significant positive association of PADI4 haplotype 4 with RA could be demonstrated. Other PADI4 haplotypes did not differ significantly between patients and controls. Regarding the individual PADI4 variants, padi4_89 (A-->G), padi4_90 (C-->T), and padi4_94 (C-->T) were significantly associated with RA (patients, 49.5%; controls, 38.7%; odds ratio = 1.6, 95% confidence interval = 1.1-2.3). Considering novel PADI4 variants located in or near to exons 2, 3, and 4, no quantitative or qualitative differences between RA patients (8.8%) and healthy controls (10.8%) could be demonstrated. While the PADI4 genotype did not influence disease activity and the anti-cyclic citrullinated peptide antibody level, the presence of the HLA-DRB1 shared epitope was significantly associated with higher anti-cyclic citrullinated peptide antibody levels (P = 0.033). The results of this small case-control study support the hypothesis that variability of the PADI4 gene may influence susceptibility to RA in the German population. Quantitative or qualitative differences in previously undefined PADI4 variants between patients and controls could not be demonstrated.

Adolescent↗
PubMed2006

Gene polymorphisms implicated in influencing susceptibility to venous and arterial thromboembolism: frequency distribution in a healthy German population.

Evolvement and progression of cardiovascular diseases affecting the venous and arterial system are influenced by a multitude of environmental and hereditary factors. Many of these hereditary factors consist of defined gene polymorphisms, such as single nucleotide polymorphisms (SNPs) or insertion-deletion polymorphisms, which directly or indirectly affect the hemostatic system. The frequencies of individual hemostatic gene polymorphisms in different normal populations are well defined. However, descriptions of patterns of genetic variability of a larger extent of different factors of hereditary hypercoagulability in single populations are scarce. The aim of this study was i) to give a detailed description of the frequencies of factors of hereditary thrombophilia and their combinations in a German population (n = 282) and ii) to compare their distributions with those reported for other regions. Variants of coagulation factors [factor V 1691G>A (factor V Leiden), factor V 4070A>G (factor V HR2 haplotype), factor VII Arg353Gln, factor XIII Val34Leu, beta-fibrinogen -455G>A, prothrombin 20210G>A], coagulation inhibitors [tissue factor pathway inhibitor 536C>T, thrombomodulin 127G>A], fibrinolytic factors [angiotensin converting enzyme intron 16 insertion/deletion, factor VII-activating protease 1601G>A (FSAP Marburg I), plasminogen activator inhibitor 1-675 insertion/deletion (5G/4G), tissue plasminogen activator intron h deletion/insertion], and other factors implicated in influencing susceptibility to thromboembolic diseases [apolipoprotein E2/E3/E4, glycoprotein Ia 807C>T, methylenetetrahydrofolate reductase 677C>T] were included. The distribution of glycoprotein Ia 807C>T deviated significantly from the Hardy-Weinberg equilibrium, and a comparison with previously published data indicates marked region and ethnicity dependent differences in the genotype distributions of some other factors.

Arterial Occlusive Diseases↗
PubMed2004

Marburg I polymorphism of factor VII-activating protease is associated with idiopathic venous thromboembolism.

The factor VII-activating protease (FSAP) variant Marburg I is known to attenuate the profibrinolytic system in vitro and was recently shown to be a significant predictor for the evolution and progression of carotid stenosis. The objective of this case-control study was to assess FSAP Marburg I's role in the occurrence of venous thromboembolism (VTE). The frequency of FSAP Marburg I was significantly increased in patients with a history of VTE (17 of 213 patients, 8.0%, P = .014) or idiopathic VTE (12 of 103 patients, 11.7%, P = .002) compared to healthy controls (5 of 213 controls, 2.3%). Logistic regression analysis confirmed FSAP Marburg I to be an independent risk factor for VTE (odds ratio, 3.5; 95% confidence interval [CI], 1.2-10.0) and idiopathic VTE (odds ratio, 6.2; 95% CI, 2.0-18.9).

Adolescent↗
PubMed2004

High variability of peptidylarginine deiminase 4 (PADI4) in a healthy white population: characterization of six new variants of PADI4 exons 2-4 by a novel haplotype-specific sequencing-based approach.

Seven single nucleotide polymorphisms (SNPs) of the peptidylarginine deiminase 4 (PADI4) gene have recently been reported to be strongly associated with rheumatoid arthritis in Japanese individuals. These SNPs are located in or close to exons 2-4 of PADI4 and are organized in at least four different haplotypes. However, a detailed sequencing-based characterization of the PADI4 gene in other populations is still lacking. We therefore analyzed exons 2-4 of the PADI4 gene in 102 healthy white Germans individuals by DNA sequencing and characterized new variants and haplotypes by a novel haplotype-specific sequencing-based approach. The haplotypes 2/3 (padi4_89*G, padi4_90*T, padi4_92*G, padi4_94*T, padi4_104*T, padi4_95*C, padi4_96*C), and haplotype 4 (padi4_89*G, padi4_90*T, padi4_92*G, padi4_94*T, padi4_104*C, padi4_95*G, padi4_96*T) conferring susceptibility to rheumatoid arthritis were detected at frequencies of 30.9% and 7.8%, respectively. In addition, three novel coding SNPs in exons 2, 3, and 4, and three SNPs in introns 2 and 3 located near the exon-intron boundaries were identified in 11 individuals (10.8%). The so-called nonsusceptibility haplotype 1 (padi4_89*A, padi4_90*C, padi4_92*C, padi4_94*C, padi4_104*C, padi4_95*G, padi4_96*T) occurred at a frequency of 58.3%. Additionally, we identified a closely related novel haplotype, haplotype 1B (2.9%), that differs from haplotype 1 only by padi4_92*G/padi4_96*C. This haplotype was not described in the Japanese population. Our results indicate that the PADI4 gene exhibits a remarkable variability and a rather complex haplotypic organization. Further studies on disease association of PADI4 should be performed by haplotype-specific sequencing-based approaches to identify the exact genotype of the PADI4 fragment of interest.

Exons↗
PubMed2003

Screening for multiple hereditary hypercoagulability factors using the amplification refractory mutation system.

Many hereditary factors have been implicated in the development of arterial and/or venous thromboembolic diseases. A number of these risk factors can be identified by the amplification refractory mutation system (ARMS). However, the underlying technical conditions for performing ARMS are highly variable, and depend on which risk factors are being analyzed. We have now developed a novel ARMS-based system to simultaneously screen for multiple hypercoagulability factors under identical PCR conditions. This can greatly simplify the process of screening for hereditary hypercoagulability.

Base Sequence↗