Manfred Schürmann

Universität zu Lübeck, Lübeck Hansestadt, Schleswig-Holstein, Germany

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Publications (35)242.09 Total impact

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    ABSTRACT: To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci. Altogether the study population comprised over 19,000 individuals. In a two-stage design, 1726 German sarcoidosis cases and 5482 controls were genotyped for 128,705 SNPs using the Illumina Immunochip for the screening step. The remaining 3955 cases, 7514 controls and 684 parents of affected offspring were used for validation and replication of 44 candidate and 2 established risk SNPs. Four novel susceptibility loci were identified with genome-wide significance in the European case control populations, located on chromosomes 12q24.12 (rs653178; ATXN2/SH2B3), 5q33.3 (rs4921492; IL12B), 4q24 (rs223498; MANBA/NFKB1) and 2q33.2 (rs6748088; FAM117B). We further defined three independent association signals in the HLA-region with genome-wide significance, peaking in the BTNL2 promoter region (rs5007259), at HLA-B (rs4143332/HLA-B*0801) and at HLA DPB1 (rs9277542), and found another novel independent signal near IL23R (rs12069782) on chromosome 1p31.3. Functional predictions and protein network analyses suggest a prominent role of the drug-targetable IL23/Th17-signaling pathway in the genetic etiology of sarcoidosis. Our findings reveal a substantial genetic overlap of sarcoidosis with diverse immune-mediated inflammatory disorders, which could be of relevance for the clinical application of modern therapeutics.
    American Journal of Respiratory and Critical Care Medicine 06/2015; 192(6). DOI:10.1164/rccm.201503-0418OC · 13.00 Impact Factor
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    ABSTRACT: Sarcoidosis is a systemic inflammatory disease of unknown etiology, influenced by genetic and environmental factors. However, the loci so far identified for sarcoidosis explain only a part of its assumed heritability.To identify further susceptibility loci, we performed a genome-wide association analysis using the Affymetrix 6.0 Human GeneChip followed by validation and replication stages.After quality control, 637 cases, 1,233 controls and 677,619 SNPs were available for an initial screening. 99 SNPs were selected for validation in an independent study panel (1,664 patients, 2,932 controls).SNP rs1050045 was significantly associated with sarcoidosis (corrected p=0.0215) in the validation panel and yielded a p value of 9.22×10(-8) (OR=1.24) in the meta-analysis of the screening and validation stage. A meta-analysis of three populations from Germany, Czech Republic and Sweden confirmed this finding (p=0.024; OR=1.14). Fine-mapping and mRNA expression studies pointed to osteosarcoma amplified 9 (OS9) as the most likely candidate for the underlying risk factor.The OS9 protein plays an important role in the ER-associated protein degradation and acts during Toll-like receptor induced activation of myeloid cells. Expression analyses of OS9 mRNA provide evidence for a functional mechanism underlying the detected association signal.
    European Respiratory Journal 08/2012; 41(4). DOI:10.1183/09031936.00033812 · 7.64 Impact Factor
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    ABSTRACT: RATIONALE: Sarcoidosis is a complex inflammatory disease with a heterogeneous clinical picture. Amongst others, an acute and chronic clinical course can be distinguished, for which specific genetic risk factors are known. OBJECTIVES: In order to identify additional risk loci for sarcoidosis and its acute and chronic subforms, we analyzed imputed data from a genome-wide association scan (GWAS) for these phenotypes. METHODS: After quality control, the GWAS comprised nearly 1.3 million imputed single nucleotide polymorphisms based on an Affymetrix 6.0 Gene Chip dataset of 564 German sarcoidosis cases, including 176 acute and 354 chronic cases and 1575 controls. MAIN RESULTS: We identified chromosome 11q13.1 (rs479777) as a novel locus influencing susceptibility to sarcoidosis with genome-wide significance. The marker was significantly associated in three distinct German case-control populations and in an additional German family sample with ORs ranging from 0.67 to 0.77. This finding was further replicated in two independent European case-control populations from the Czech Republic (OR = 0.75) and from Sweden (OR = 0.79). In a meta-analysis of the included European case-control samples the marker yielded a p value of 2.68x10(-18). The locus was previously reported to be associated with Crohn´s disease, alopecia areata, leprosy and psoriasis. For sarcoidosis, fine-mapping and expression analysis suggest KCNK4, PRDX5, PCLB3 and, most promising, CCDC88B, as candidates for the underlying risk gene in the associated region. CONCLUSION: This study provides striking evidence for association of chromosome 11q13.1 with sarcoidosis in Europeans, and thus identified a further genetic risk locus shared by sarcoidosis, Crohn´s disease and psoriasis.
    American Journal of Respiratory and Critical Care Medicine 07/2012; 186(9). DOI:10.1164/rccm.201204-0708OC · 13.00 Impact Factor
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    ABSTRACT: Sarcoidosis is a complex systemic inflammatory disease of unknown aetiology that is influenced by a variety of genetic and environmental factors. To identify further susceptibility loci for sarcoidosis, a genome-wide association study (GWAS) was conducted in 381 patients and 392 control individuals based on Affymetrix 100k GeneChip data. The top 25 single-nucleotide polymorphisms (SNPs) were selected for validation in an independent study panel (1,582 patients versus 1,783 controls). Variant rs10484410 on chromosome 6p12.1 was significantly associated, with a Bonferroni-corrected p-value of 2.90 × 10⁻² in the validation sample and a nominal p-value of 2.64 × 10⁻⁴ in the GWAS. Extensive fine mapping of the novel locus narrowed down the signal to a region comprising the genes BAG2, C6orf65, KIAA1586, ZNF451 and RAB23. Verification of the sarcoidosis-associated nonsynonymous SNP rs1040461 in a further independent case-control sample and quantitative mRNA expression studies point to the RAB23 gene as the most likely risk factor. RAB23 is proposed to be involved in antibacterial defence processes and regulation of the sonic hedgehog signalling pathway. The identified association of the 6p12.1 locus with sarcoidosis implicates this locus as a further susceptibility factor and RAB23 as a potential signalling component that may open up new perspectives in the pathophysiology of sarcoidosis.
    European Respiratory Journal 05/2011; 38(5):1127-35. DOI:10.1183/09031936.00001711 · 7.64 Impact Factor
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    ABSTRACT: Sarcoidosis is a complex granulomatous inflammatory disorder that shares several clinical and pathogenic features with inflammatory bowel disease (IBD). Postulating a common genetic basis of inflammatory diseases, we tested 106 single-nucleotide polymorphisms (SNPs) that are known or have been suggested to be associated with IBD for a potential association with sarcoidosis and its acute and chronic subphenotypes. We genotyped 1,996 German sarcoidosis patients, comprising 648 acutely and 1,161 chronically affected individuals, 2,622 control subjects, and 342 German trios with affected offspring using SNPlex™ technology. The nonsynonymous SNP rs11209026 (Arg381Gln) in the interleukin (IL)-23 receptor (IL23R) gene was associated with chronic sarcoidosis (OR 0.63; p = 5.58×10(-5)), which was supported by the result of a transmission disequilibrium test analysis in the independent family sample (OR 0.50; p = 0.031). Marker rs12035082 located at chromosome 1q24.3 was found to be associated with the acute subphenotype (OR 1.36; p = 6.80×10(-7)) and rs916977 (HERC2 locus; OR 1.30; p = 4.49×10(-5)) was associated with sarcoidosis. Our results highlight the potential importance of the IL-23 signalling pathway for the development of chronic sarcoidosis. The finding links sarcoidosis pathogenesis to other inflammatory conditions and may contribute to new hypotheses on disease mechanisms.
    European Respiratory Journal 03/2011; 37(3):610-6. DOI:10.1183/09031936.00049410 · 7.64 Impact Factor
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    ABSTRACT: Sarcoidosis (SA) is a systemic granulomatous inflammatory disorder with complex etiology and strong clustering in families. Genome-wide association studies have been successful in the identification of common risk variants for the disease. To reveal susceptibility variants with low frequencies but strong effects, we performed a genome-wide linkage scan in a large sample of SA families. We genotyped 528 members of 181 German SA families for 3,882 single nucleotide polymorphism assays from the SNPlex System Human Linkage Mapping Set 4K. Nonparametric linkage analysis revealed one region of suggestive linkage on chromosome 12p13.31 at 20 cM (logarithm of odds [LOD] = 2.53; local P value = .0003) and another linkage peak of nearly suggestive linkage on 9q33.1 at 134 cM (LOD = 2.12; local P value = .0009). The latter has been reported to show suggestive evidence for linkage in a sample of 229 African American SA families previously. Analysis of acute and chronically affected families revealed a subphenotype-specific linkage pattern and an additional, nearly suggestive linkage peak on chromosome 16p13.11 at 38 cM (LOD = 2.09; local P value = .001), which was confined to acute SA. Our results propose that the respective regions might harbor yet-unidentified, possibly subphenotype-specific risk factors for the disease (eg, with immune-related functions like the tumor necrosis factor receptor 1). They should be proved to be important for SA pathogenesis and investigated in detail with an emphasis on rare variants. Subphenotype-specific risk factors might serve for prognosis of the clinical course of the disease.
    Chest 02/2010; 138(1):151-7. DOI:10.1378/chest.09-2526 · 7.48 Impact Factor
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    ABSTRACT: Sarcoidosis is a multifactorial and polygenic disorder. The current knowledge of its genetics will be presented and discussed in the context of other granulomatous disorders of known and unknown aetiology. The differing and common features of these disorders lead to the perspective that in near future it will be possible to establish genotype-phenotype correlations which will predict the course and therapy response in an individual case.
    Pneumologie 04/2009; 63(3):166-75.

  • Pneumologie 01/2009; 63(03):166-175. DOI:10.1055/s-0028-1100825
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    ABSTRACT: Sarcoidosis is a multigenic and multifactorial disease. Predisposing genes have been identified and fast progress in molecular technologies including systematic genome-wide association studies and large-scale resequencing will aid the discovery of further risk loci and variants. The exploration of the molecular epidemiology of genetic variants in the pathogenesis of sarcoidosis will allow an assessment of their prognostic usefulness. To this end, different granulomatous disorders of known and unknown etiology should be investigated jointly by genetic, immunobiological, and proteomic approaches. The definition of individual genetic risk profiles in sarcoidosis and other chronic inflammatory disorders seems achievable and a useful route for clinical translation.
    Clinics in Chest Medicine 10/2008; 29(3):391-414, viii. DOI:10.1016/j.ccm.2008.03.007 · 2.07 Impact Factor
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    ABSTRACT: Sarcoidosis is a complex chronic inflammatory disorder with predominant manifestation in the lung. In the first genome-wide association study (> 440,000 SNPs) of this disease, comprising 499 German individuals with sarcoidosis and 490 controls, we detected a series of genetic associations. The strongest association signal maps to the ANXA11 (annexin A11) gene on chromosome 10q22.3. Validation in an independent sample (1,649 cases, 1,832 controls) confirmed the association (SNP rs2789679: P = 3.0 x 10(-13), rs7091565: P = 1.0 x 10(-5), allele-based test). Extensive fine mapping located the association signal to a region between exon 5 and exon 14 of ANXA11. A common nonsynonymous SNP (rs1049550, C > T, [corrected] R230C) was found to be strongly associated with sarcoidosis. The GWAS lead SNP and additional risk variants in the region (rs1953600, rs2573346, rs2784773) were in strong linkage disequilibrium with rs1049550. Annexin A11 has complex and essential functions in several biological pathways, including apoptosis and proliferation.
    Nature Genetics 09/2008; 40(9):1103-6. DOI:10.1038/ng.198 · 29.35 Impact Factor
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    ABSTRACT: Crohn's disease (CD) and sarcoidosis (SA) are chronic inflammatory barrier diseases that share several clinical and immunological features, including the occurrence of granulomas. A 100k genome-wide association study with 83,360 single-nucleotide polymorphisms (SNPs) was performed on 382 CD patients, 398 SA patients, and 394 control individuals. The 24 SNPs that were most strongly associated in the combined CD/SA phenotype were selected for verification in an independent sample of 1,317 patients (660 CD and 657 SA) and 1,091 controls. The most significant association (Bonferroni corrected P = .036) was obtained at SNP rs1398024 on chromosome 10p12.2, with an odds ratio (OR) for both diseases of 0.81 (95% confidence interval [CI], 0.69-0.96) for carriership of the rarer allele A. The P value in the overall combined sample was 4.24 x 10(-6). During further follow-up, a moderate association (OR, 0.83; 95% CI, 0.72-0.96; P = .015) was observed between rs1398024 and ulcerative colitis (1,080 patients vs 1,091 controls), the second main subphenotype of inflammatory bowel disease in addition to CD. Extensive fine mapping of the 10p12.2 locus points to yet unidentified variants in the C10ORF67 gene region as the most likely underlying risk factors. Our study demonstrates that the combined analysis of different, albeit clinically related, phenotypes can lead to the identification of common susceptibility loci.
    Gastroenterology 08/2008; 135(4):1207-15. DOI:10.1053/j.gastro.2008.07.017 · 16.72 Impact Factor
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    ABSTRACT: Sarcoidosis is a multi-factorial systemic disease of granulomatous inflammation. Current concepts of the aetiology include interactions of unknown environmental triggers with an inherited susceptibility. Toll-like receptors (TLRs) are main components of innate immunity and therefore TLR genes are candidate susceptibility genes in sarcoidosis. Ten members of the human TLR gene family have been identified and mapped to seven chromosomal segments. The aim of this study was to investigate all known TLR gene loci for genetic linkage with sarcoidosis and to follow positive signals with different methods. We analysed linkage of TLR gene loci to sarcoidosis by use of closely flanking microsatellite markers in 83 families with 180 affected siblings. We found significant linkage between sarcoidosis and markers of the TLR4 gene locus on chromosome 9q (non-parametric linkage score 2.63, P = 0.0043). No linkage was found for the remaining TLR gene loci. We subsequently genotyped 1203 sarcoidosis patients from 997 families, 1084 relatives and 537 control subjects for four single nucleotide polymorphisms of TLR4, including Asp299Gly and Thr399Ile. This genotype data set was studied by case-control comparisons and transmission disequilibrium tests, but showed no significant results. In summary, TLR4 - w ith significant genetic linkage results - appears to be the most promising member of the TLR gene family for further investigation in sarcoidosis. However, our results do not confirm the TLR4 polymorphisms Asp299Gly and Thr399Ile as susceptibility markers. Our results rather point to another as yet unidentified variant within or close to TLR4 that might confer susceptibility to sarcoidosis.
    Clinical & Experimental Immunology 07/2008; 152(3):423-31. DOI:10.1111/j.1365-2249.2008.03621.x · 3.04 Impact Factor
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    ABSTRACT: C-C chemokine receptors have been suggested to play an important role in sarcoidosis pathogenesis. Previous investigation of the C-C chemokine receptor 5 (CCR5) gene revealed the association of the HHC haplotype with "persistent lung involvement" in two European sarcoidosis populations. Based on this finding, we investigated a possible association of the HHC haplotype and its marker alleles in an extended German sarcoidosis sample that comprised 995 German sarcoidosis families including individuals with the chronic and acute form of the disease, further refined to patients with and without Löfgren's syndrome. We genotyped this sample and 538 healthy control subjects for 8 single nucleotide polymorphisms (SNPs) that define the HHC haplotype in the CCR5 genomic region. Analysis of 3 sarcoidosis phenotypes (chronic, acute and Löfgren's syndrome) revealed that the HHC haplotype was not associated with chronic sarcoidosis although a substantial overlap can be assumed between the chronic form examined in our study and "persistent parenchymal lung involvement", the phenotype for which an association was previously established. However, 2 marker alleles in the putative CCR5 promoter, which are part of the HHC haplotype, are associated with Löfgren's syndrome. Strikingly, the association is restricted to females. This finding is consistent with recently described sex-specific manifestations of Löfgren's syndrome and with previous functional studies suggesting an estrogen-dependent CCR5 expression. The female-specific association of SNPs in the putative CCR5 promoter region with Löfgren's syndrome raises the possibility that the dysregulated, sex-specific modification of CCR5 expression could contribute to the increased risk of women to develop the disease.
    Journal of Molecular Medicine 06/2008; 86(5):553-61. DOI:10.1007/s00109-008-0315-5 · 5.11 Impact Factor
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    ABSTRACT: Chronic beryllium disease (CBD) is a rare occupational, granulomatous lung disease clinically resembling sarcoidosis. The immune response to beryllium is thought to depend on genetic susceptibility. Although a glutamic acid in position 69 of the human leukocyte antigen-DP beta chain (HLA-DPB1-Glu69) is associated with the development of CBD, it cannot fully explain susceptibility. It is likely that additionally other genes are involved in regulating the immune and inflammatory response in the pathogenesis of this disease. Functional gene polymorphisms (PMs) of the tumor necrosis factor (TNF)A and transforming growth factor (TGF) beta(1) genes are suspected to modify the course of granulomatous disorders. We analyzed the TGF-beta(1) (codon 25) PM in 59 patients with CBD and 164 matched healthy controls, from two groups of European/Israeli and United States origin. Additionally, patients were genotyped for HLA class II gene variants and the TNFA (-308) PM. The most significant results were found for the TGF-beta(1) (codon 25) PM with a shift towards the low producing non-GG genotypes in the subgroup of European and Israeli patients with CBD (62.50% vs. 13.82% in healthy controls; P<0.001). This phenomenon was not observed in the group from the United States. Moreover, TGF-beta(1) (codon 25) PM genotype frequencies from United States CBD patients differed significantly from those of European and Israeli patients. In contrast, increased frequencies for the high producing TNFA2 allele were found only in the patients from the United States (28.20% vs. 8.96% in healthy controls; P<0.005) but not in the group of Europe and Israel. In conclusion, the increase in TGF-beta(1) (codon 25) PM genotype frequency associated with a low TGF-beta release suggests that immunoregulatory cytokines such as TGF-beta are involved in the pathogenesis of CBD. Moreover, based on the interaction of gene PMs associated with the control of the immune response, such as TNF-alpha and TGF-beta(1), with a specific immune response gene such as HLA-DPB1-Glu69 or other HLA-class II PMs driving the immune response to Be, the present data suggest that a combination of different genetic backgrounds determine susceptibility for the same immunopathological reaction and disease.
    Journal of Molecular Medicine 06/2005; 83(5):397-405. DOI:10.1007/s00109-004-0626-0 · 5.11 Impact Factor
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    ABSTRACT: Prevailing models of sarcoidosis pathogenesis involve the activation of alveolar macrophages, aggregation of CD4+ T lymphocytes, and their accumulation in epithelioid cell granulomas. Increasing evidence suggests that each of these steps is modified by the host genetic constitution. Consequently, candidate susceptibility genes have been selected based on their potential function under this model. The C-C chemokine receptor 2 (CCR2) is involved in Th1 immune activity by recruiting competent cells and possibly by balancing response. CCR2 gene variants have been shown to be associated with sarcoidosis or, more specifically, with Löfgren's syndrome, a distinct form of acute sarcoidosis. We have studied three CCR2 gene polymorphisms (c.190G>A, c.840C>T, and c.4385A>T) in an extended sample of 1,203 patients with sarcoidosis and their relatives. Case-control comparisons and family-based genetic analyses did not support previous findings of an association between CCR2 gene variability and the risk of sarcoidosis. However, they confirmed linkage disequilibrium and showed positive linkage results (p = 0.034) and therefore suggest a susceptibility gene in the surrounding chromosomal region.
    American Journal of Respiratory and Critical Care Medicine 06/2005; 171(10):1136-41. DOI:10.1164/rccm.200405-658OC · 13.00 Impact Factor
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    ABSTRACT: Sarcoidosis is a polygenic immune disorder with predominant manifestation in the lung. Genome-wide linkage analysis previously indicated that the extended major histocompatibility locus on chromosome 6p was linked to susceptibility to sarcoidosis. Here, we carried out a systematic three-stage SNP scan of 16.4 Mb on chromosome 6p21 in as many as 947 independent cases of familial and sporadic sarcoidosis and found that a 15-kb segment of the gene butyrophilin-like 2 (BTNL2) was associated with the disease. The primary disease-associated variant (rs2076530; P(TDT) = 3 x 10(-6), P(case-control) = 1.1 x 10(-8); replication P(TDT) = 0.0018, P(case-control) = 1.8 x 10(-6)) represents a risk factor that is independent of variation in HLA-DRB1. BTNL2 is a member of the immunoglobulin superfamily and has been implicated as a costimulatory molecule involved in T-cell activation on the basis of its homology to B7-1. The G --> A transition constituting rs2076530 leads to the use of a cryptic splice site located 4 bp upstream of the affected wild-type donor site. Transcripts of the risk-associated allele have a premature stop in the spliced mRNA. The resulting protein lacks the C-terminal IgC domain and transmembrane helix, thereby disrupting the membrane localization of the protein, as shown in experiments using green fluorescent protein and V5 fusion proteins.
    Nature Genetics 05/2005; 37(4):357-64. DOI:10.1038/ng1519 · 29.35 Impact Factor
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    ABSTRACT: Sarcoidosis, Blau syndrome and Crohn's disease are complex disorders, characterised by granulomatous inflammation affecting a variety of organs. Mutations of the CARD15 gene, on chromosome 16, have been shown to contribute significantly to Crohn's disease and to cause Blau syndrome. These factors prompted the current authors to study CARD15 mutations in sarcoidosis. A total of 138 families were genotyped, including 302 patients with sarcoidosis and 127 patients without a family history of sarcoidosis (together with their parents), for four main coding CARD15 polymorphisms associated with increased risk of Crohn's disease. Furthermore, the gene segment that harbours Blau syndrome mutations was sequenced in 39 selected patients from 39 families with affected siblings identical for one or two parental chromosomes 16s and in eight patients from multi-case families. None of the reported Blau syndrome mutations and no new sequence alterations were found. There was an increased frequency of transmission of the rare allele of the polymorphic sites 802C>T (SNP5) and 2722G>C (SNP12) in at least one of the two study groups. In conclusion, CARD15 mutations, which are important in Crohn's disease and Blau syndrome, play no major role in sarcoidosis in this study population. However, these mutations could be of limited importance, especially in patients without a family history of sarcoidosis.
    European Respiratory Journal 12/2003; 22(5):748-54. DOI:10.1183/09031936.03.00040602 · 7.64 Impact Factor
  • Manfred Schürmann ·
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    ABSTRACT: Sarcoidosis is a systemic disorder of granulomatous inflammation that primarily affects the lung and lymph system, although all organs can be involved. Two principal presentations of the disorder can be defined; an acute form, often with short duration and complete restitution, and a more insidious course with multiorgan involvement and a higher risk of progressive organ damage. Sarcoidosis affects mainly young adults. The etiology of sarcoidosis is unknown, and current concepts assume one or more environmental triggers that start in a host with an inherited susceptibility to a dysbalanced immune response. Candidate susceptibility genes include genes with a function in antigen recognition, T cell activation, T-helper 1/2 (TH1/TH2) cell balance, and granuloma formation. A few genetic linkage analyses and numerous association studies with a focus on the region of the major histocompatibility complex genes have been performed, which have so far yielded no breakthrough. They have, rather, verified the assumption of a complex and possibly heterogeneous character of the genetics of sarcoidosis.
    Seminars in Respiratory and Critical Care Medicine 05/2003; 24(2):213-22. DOI:10.1055/s-2003-39020 · 2.71 Impact Factor
  • Manfred Schürmann ·
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    ABSTRACT: Angiotensin converting enzyme (ACE) is a metallopeptidase with a key function in the regulation of blood pressure and volume. The ACE1 gene, on chromosome 17, contains a insertion/deletion (I/D) polymorphism in intron 16. The D allele of this polymorphism is linked with raised serum ACE (sACE) levels. Sarcoidosis is a systemic disease of granulomatous inflammation that primarily affects the lung and lymph system. It is often accompanied by elevated sACE related to ACE production from granuloma cells. The ACE I/D polymorphism has been tested for association or linkage with the risk of sarcoidosis. Though published results are conflicting, there seems to be suggestive evidence of a minor pro-inflammatory influence of the ACE D allele in sarcoidosis. At present, a more accurate interpretation of sACE levels in diagnosis and monitoring of sarcoidosis seems to be the main value of ACE I/D genotyping.
    American Journal of PharmacoGenomics 02/2003; 3(4):233-43. DOI:10.2165/00129785-200303040-00002
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    Manfred Schürmann · Melanie Albrecht · Eberhard Schwinger · Manfred Stuhrmann ·
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    ABSTRACT: Sarcoidosis is a complex disease of multiorgan granulomatous inflammation. Genetic susceptibility is involved in the pathogenesis of the disorder. Two successive studies from Italy have shown a high frequency of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients suffering from sarcoidosis. We have genotyped a panel of 63 families with two or more affected siblings for the CFTR gene mutation R75Q, which was found to be present in three of 26 cases of the Italian study. Although R75Q was present in seven families, it was neither associated with the sarcoidosis phenotype in the German population (P=0.5), nor was it linked to sarcoidosis (P=0.54). In addition, a screening for 34 functional CFTR mutations was performed in a subset of 54 patients from 25 families. These patients were known to be concordant for at least one parental copy of the CFTR gene. With the exception of the mayor CF mutation deltaF508, which was present in three patients and absent in one patient from two families, we did not find any other CF mutation in these 54 patients. Our results do not support the hypothesis that CFTR mutations have a major influence on the pathogenesis of sarcoidosis.
    European Journal of HumanGenetics 12/2002; 10(11):729-32. DOI:10.1038/sj.ejhg.5200868 · 4.35 Impact Factor

Publication Stats

1k Citations
242.09 Total Impact Points


  • 1994-2012
    • Universität zu Lübeck
      • Institute of Human Genetics
      Lübeck Hansestadt, Schleswig-Holstein, Germany
  • 2009
    • University of Freiburg
      • Department of Pneumology
      Freiburg, Baden-Württemberg, Germany
  • 2005
    • Christian-Albrechts-Universität zu Kiel
      • Institute of Clinical Molecular Biology
      Kiel, Schleswig-Holstein, Germany
  • 2000
    • University of Münster
      • Department of Psychiatry
      Münster, North Rhine-Westphalia, Germany