Elisa Lahtela1, Annika Wennerström1, Anne Pietinalho2, Martin Petrek3, Vitezslav Kolek4, Marja-Liisa Lokki1, Olof Selroos5. 1. Transplantation Laboratory, Medicum, University of Helsinki, Finland. 2. Raasepori Health Care Centre, Raasepori, Finland. 3. Laboratory of Immunogenomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry Palacký University, Olomouc, Czech Republic. 4. Department of Respiratory Medicine and Tuberculosis, Faculty of Medicine and Dentistry Palacký University, Olomouc, Czech Republic. 5. Semeco AB, Vejbystrand, Sweden.
Abstract
Background: Sarcoidosis is a systemic inflammatory disease with unknown etiology. However, there is a strong evidence of genetic influence in sarcoidosis. Objectives: We wanted to extend our knowledge of the role of the whole ACE gene, not only insertion/deletion (I/D) polymorphism, in a Finnish sarcoidosis population by genotyping the ACE gene region from 5' upstream to the 3' downstream. Methods: We genotyped 29 single nucleotide polymorphisms (SNPs) spanning the ACE gene from 188 sarcoidosis patients (resolved disease, n=90; persistent disease, n=98) and from 150 controls. These SNPs included tag SNP rs4343 for I/D polymorphism. To replicate the study we genotyped 11 of these SNPs from 139 Czech sarcoidosis patients (resolved disease, n=47; persistent disease, n=92) and 176 healthy controls. Results: No association was detected between I/D genotypes and disease susceptibility or prognosis. We found a novel SNP (rs9905945) in the 5'upstream region of the ACE gene to be moderately associated with favourable disease prognosis in Finnish patients [p=0.035, OR=2.034 (95%CI 1.045-3.960)]. However, in the replication study in Czechs, the SNP rs9905945 did not show association with prognosis of sarcoidosis. Conclusions: This study further characterizes genetic distinctions between Finnish sarcoidosis patients with different prognosis and population-specific genotype distribution of ACE variants. Nevertheless it seems that variants in the ACE gene do not considerably influence the course of the disease in Finnish sarcoidosis patients. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 104-114). Copyright:
Background: Sarcoidosis is a systemic inflammatory disease with unknown etiology. However, there is a strong evidence of genetic influence in sarcoidosis. Objectives: We wanted to extend our knowledge of the role of the whole ACE gene, not only insertion/deletion (I/D) polymorphism, in a Finnish sarcoidosis population by genotyping the ACE gene region from 5' upstream to the 3' downstream. Methods: We genotyped 29 single nucleotide polymorphisms (SNPs) spanning the ACE gene from 188 sarcoidosispatients (resolved disease, n=90; persistent disease, n=98) and from 150 controls. These SNPs included tag SNP rs4343 for I/D polymorphism. To replicate the study we genotyped 11 of these SNPs from 139 Czech sarcoidosispatients (resolved disease, n=47; persistent disease, n=92) and 176 healthy controls. Results: No association was detected between I/D genotypes and disease susceptibility or prognosis. We found a novel SNP (rs9905945) in the 5'upstream region of the ACE gene to be moderately associated with favourable disease prognosis in Finnish patients [p=0.035, OR=2.034 (95%CI 1.045-3.960)]. However, in the replication study in Czechs, the SNP rs9905945 did not show association with prognosis of sarcoidosis. Conclusions: This study further characterizes genetic distinctions between Finnish sarcoidosispatients with different prognosis and population-specific genotype distribution of ACE variants. Nevertheless it seems that variants in the ACE gene do not considerably influence the course of the disease in Finnish sarcoidosispatients. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 104-114). Copyright:
Authors: D S McGrath; P J Foley; M Petrek; L Izakovicova-Holla; V Kolek; S Veeraraghavan; P A Lympany; P Pantelidis; A Vasku; A U Wells; K I Welsh; R M Du Bois; V Dolek Journal: Am J Respir Crit Care Med Date: 2001-07-15 Impact factor: 21.405