Freitag-Wolf, Sandra and Schupp, Jonas C. and Frye, Bjoern C. and Fischer, Annegret and Anwar, Raihanatul and Kieszko, Robert and Mihailovic-Vucinic, Violeta and Milanowski, Janusz and Jovanovic, Dragana and Zissel, Gernot and Bargagli, Elena and Rottoli, Paola and Bumbacea, Dragos and Jonkers, Rene and Ho, Ling-Pei and Gaede, Karoline I. and Dubaniewicz, Anna and Marshall, Ben G. and Guenther, Andreas and Petrek, Martin and Keane, Michael P. and Haraldsdottir, Sigridur O. and Bonella, Francesco and Grah, Christian and Peros-Golubicic, Tatjana and Kadija, Zamir and Pabst, Stefan and Grohe, Christian and Strausz, Janos and Safrankova, Martina and Millar, Ann and Homolka, Jiri and Wuyts, Wim A. and Spencer, Lisa G. and Pfeifer, Michael and Valeyre, Dominique and Poletti, Venerino and Wirtz, Hubertus and Prasse, Antje and Schreiber, Stefan and Dempfle, Astrid and Mueller-Quernheim, Joachim (2023) Genetic and geographic influence on phenotypic variation in European sarcoidosis patients. FRONTIERS IN MEDICINE, 10: 1218106. ISSN , 2296-858X
Full text not available from this repository.Abstract
Introduction Sarcoidosis is a highly variable disease in terms of organ involvement, type of onset and course. Associations of genetic polymorphisms with sarcoidosis phenotypes have been observed and suggest genetic signatures.Methods After obtaining a positive vote of the competent ethics committee we genotyped 1909 patients of the deeply phenotyped Genetic-Phenotype Relationship in Sarcoidosis (GenPhenReSa) cohort of 31 European centers in 12 countries with 116 potentially disease-relevant single-nucleotide polymorphisms (SNPs). Using a meta-analysis, we investigated the association of relevant phenotypes (acute vs. sub-acute onset, phenotypes of organ involvement, specific organ involvements, and specific symptoms) with genetic markers. Subgroups were built on the basis of geographical, clinical and hospital provision considerations.Results In the meta-analysis of the full cohort, there was no significant genetic association with any considered phenotype after correcting for multiple testing. In the largest sub-cohort (Serbia), we confirmed the known association of acute onset with TNF and reported a new association of acute onset an HLA polymorphism. Multi-locus models with sets of three SNPs in different genes showed strong associations with the acute onset phenotype in Serbia and Lublin (Poland) demonstrating potential region-specific genetic links with clinical features, including recently described phenotypes of organ involvement.Discussion The observed associations between genetic variants and sarcoidosis phenotypes in subgroups suggest that gene-environment-interactions may influence the clinical phenotype. In addition, we show that two different sets of genetic variants are permissive for the same phenotype of acute disease only in two geographic subcohorts pointing to interactions of genetic signatures with different local environmental factors. Our results represent an important step towards understanding the genetic architecture of sarcoidosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; RISK; POLYMORPHISMS; DISEASE; ANXA11; genetic polymorphism; genetic risk factors; sarcoidosis; genotype-phenotype-relationship; region-specific genetic links |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Apr 2024 13:30 |
| Last Modified: | 19 Apr 2024 13:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60941 |
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