SNP Variants in Major Histocompatibility Complex Are Associated with Sarcoidosis Susceptibility-A Joint Analysis in Four European Populations
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F17%3A73580485" target="_blank" >RIV/61989592:15110/17:73580485 - isvavai.cz</a>
Result on the web
<a href="http://journal.frontiersin.org/article/10.3389/fimmu.2017.00422/full" target="_blank" >http://journal.frontiersin.org/article/10.3389/fimmu.2017.00422/full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fimmu.2017.00422" target="_blank" >10.3389/fimmu.2017.00422</a>
Alternative languages
Result language
angličtina
Original language name
SNP Variants in Major Histocompatibility Complex Are Associated with Sarcoidosis Susceptibility-A Joint Analysis in Four European Populations
Original language description
Sarcoidosis is a multiorgan inflammatory disorder with heritability estimates up to 66%. Previous studies have shown the major histocompatibility complex (MHC) region to be associated with sarcoidosis, suggesting a functional role for antigen-presenting molecules and immune mediators in the disease pathogenesis. To detect variants predisposing to sarcoidosis and to identify genetic differences between patient subgroups, we studied four genes in the MHC Class III region (LTA, TNF, AGER, BTNL2) and HLA-DRA with tag-SNPs and their relation to HLA-DRB1 alleles. We present results from a joint analysis of four study populations (Finnish, Swedish, Dutch, and Czech). Patients with sarcoidosis (n = 805) were further subdivided based on the disease activity and the presence of Löfgren's syndrome. In a joint analysis, seven SNPs were associated with non-Löfgren sarcoidosis (NL; the strongest association with rs3177928, P = 1.79E-07, OR = 1.9) and eight with Löfgren's syndrome [Löfgren syndrome (LS); the strongest association with rs3129843, P = 3.44E-12, OR = 3.4] when compared with healthy controls (n = 870). Five SNPs were associated with sarcoidosis disease course (the strongest association with rs3177928, P = 0.003, OR = 1.9). The high linkage disequilibrium (LD) between SNPs and an HLA-DRB1 challenged the result interpretation. When the SNPs and HLA-DRB1 alleles were analyzed together, independent association was observed for four SNPs in the HLA-DRA/BTNL2 region: rs3135365 (NL; P = 0.015), rs3177928 (NL; P < 0.001), rs6937545 (LS; P = 0.012), and rs5007259 (disease activity; P = 0.002). These SNPs act as expression quantitative trait loci (eQTL) for HLA-DRB1 and/or HLA-DRB5. In conclusion, we found novel SNPs in BTNL2 and HLA-DRA regions associating with sarcoidosis. Our finding further establishes that polymorphisms in the HLA-DRA and BTNL2 have a role in sarcoidosis susceptibility.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
<a href="/en/project/LO1304" target="_blank" >LO1304: Support of suistainability of the Institute of Molecular and Translational Medicine</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Frontiers in Immunology
ISSN
1664-3224
e-ISSN
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Volume of the periodical
8
Issue of the periodical within the volume
19 April 2017
Country of publishing house
CH - SWITZERLAND
Number of pages
12
Pages from-to
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UT code for WoS article
000399426600001
EID of the result in the Scopus database
2-s2.0-85018451937