Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients

<p>Abstract</p> <p>Background</p> <p>A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sampl...

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Main Authors: Nisell Magnus, Darlington Pernilla, Brynedal Boel, Grunewald Johan, Cederlund Kerstin, Hillert Jan, Eklund Anders
Format: Article
Language:English
Published: BMC 2010-02-01
Series:Respiratory Research
Online Access:http://respiratory-research.com/content/11/1/25
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author Nisell Magnus
Darlington Pernilla
Brynedal Boel
Grunewald Johan
Cederlund Kerstin
Hillert Jan
Eklund Anders
author_facet Nisell Magnus
Darlington Pernilla
Brynedal Boel
Grunewald Johan
Cederlund Kerstin
Hillert Jan
Eklund Anders
author_sort Nisell Magnus
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping.</p> <p>Subjects and methods</p> <p>In this study we HLA typed a large patient population (n = 754) recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS) (n = 302) and those without (non-Löfgren's) (n = 452), and the majority of them were clinically classified into those with recovery within two years (resolving) and those with signs of disease for more than two years (non-resolving). PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366) served as controls.</p> <p>Results</p> <p>There was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 × 10<sup>-36</sup>). Most notably, DRB1*01, DRB1*03 and DRB1*14, clearly differed in LS and non-LS patients. In relation to disease course, DRB1*07, DRB1*14 and DRB1*15 generally associated with, while DRB1*01 and DRB1*03 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB1*03 (good prognosis) dominated over that of DRB1*15 (bad prognosis).</p> <p>Conclusions</p> <p>We found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.</p>
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spelling doaj.art-1f98bae7201b43bdaa0ea3c80c3f55e62022-12-22T01:20:42ZengBMCRespiratory Research1465-99212010-02-011112510.1186/1465-9921-11-25Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patientsNisell MagnusDarlington PernillaBrynedal BoelGrunewald JohanCederlund KerstinHillert JanEklund Anders<p>Abstract</p> <p>Background</p> <p>A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping.</p> <p>Subjects and methods</p> <p>In this study we HLA typed a large patient population (n = 754) recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS) (n = 302) and those without (non-Löfgren's) (n = 452), and the majority of them were clinically classified into those with recovery within two years (resolving) and those with signs of disease for more than two years (non-resolving). PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366) served as controls.</p> <p>Results</p> <p>There was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 × 10<sup>-36</sup>). Most notably, DRB1*01, DRB1*03 and DRB1*14, clearly differed in LS and non-LS patients. In relation to disease course, DRB1*07, DRB1*14 and DRB1*15 generally associated with, while DRB1*01 and DRB1*03 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB1*03 (good prognosis) dominated over that of DRB1*15 (bad prognosis).</p> <p>Conclusions</p> <p>We found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.</p>http://respiratory-research.com/content/11/1/25
spellingShingle Nisell Magnus
Darlington Pernilla
Brynedal Boel
Grunewald Johan
Cederlund Kerstin
Hillert Jan
Eklund Anders
Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients
Respiratory Research
title Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients
title_full Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients
title_fullStr Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients
title_full_unstemmed Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients
title_short Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients
title_sort different hla drb1 allele distributions in distinct clinical subgroups of sarcoidosis patients
url http://respiratory-research.com/content/11/1/25
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