Familial vs. sporadic sarcoidosis: BTNL2 polymorphisms, clinical presentations, and outcomes in a French cohort.

Yves Pacheco,Gsf Group ,Pascal Roy,Diane Bouvry,Pascal Sève,Chahira Khouatra,Raphaelle Lamy,Claire Bardel,Laurent Pérard,Dominique Israël-Biet,Serge Lebecque,Nathalie Freymond,Alain Calender,Mad-Hélénie Elsensohn,Hilario Nunes,Dominique Valeyre,Benoît Wallaert,Gilles Devouassoux,Vincent Cottin

doi:10.1186/s13023-016-0546-4

Abstract

BackgroundThe occurrence of familial forms of sarcoidosis (OMIM 181100) suggests a genetic predisposition. The involvement of butyrophilin-like 2 (BTNL2) gene (rs2076530 variant) has to be investigated.ResultsThe study performed independent analyses of BTNL2 polymorphism, clinical phenotypes, and outcomes in familial vs. sporadic presentations in 256 sporadic and 207 familial cases from 140 families. The logistic multivariate model showed that a young age at diagnosis and the combination of lung and skin involvement at diagnosis may distinguish sporadic from familial sarcoidosis (p = 0.016 and p = 0.041). We observed also that Sarcoid Clinical Activity Classification (SCAC) profiles were significantly different between familial and sporadic cases (p = 0.0497).Variant rs2076530 was more frequent in patients than in controls (OR = 2.02; 95% CI: [1.32–3.09]) but showed no difference between sporadic and familial cases and no difference according to the clinical phenotype or the outcome.ConclusionDespite a significant difference in BTNL2 polymorphism between sarcoid patients and controls, there was no such difference between familial and sporadic sarcoidosis cases and no correlation between BTNL2 polymorphism and disease severity or outcome. Thus, BTNL2 difference cannot be considered as a key marker for disease classification or patient management.

Highlights

The occurrence of familial forms of sarcoidosis (OMIM 181100) suggests a genetic predisposition
In agreement with other studies [16, 17], we found no differences in terms of chest X-ray staging or number of organs involved at diagnosis between familial and sporadic cases but the combinations of organs involved at diagnosis was significantly different between the two groups in univariate analyses
We found a significant difference between familial and sporadic cases in terms of disease progression patterns [6] but only a trend toward a difference in the classification of outcome classification according to the duration of the disease

Summary

Introduction

The occurrence of familial forms of sarcoidosis (OMIM 181100) suggests a genetic predisposition. The involvement of butyrophilin-like 2 (BTNL2) gene (rs2076530 variant) has to be investigated. Sarcoidosis is a rare multisystemic granulomatous disorder of still unknown origin. It has various presentations, severities, treatments, and outcomes [1]. Genetic studies have searched for polymorphisms associated with the risk of developing the disease and for genotypephenotype correlations. BTNL2 (butyrophylin-like 2) has been intensively studied. A recent meta-analysis has confirmed that BTNL2 rs2076530 polymorphism contributes to the risk of sarcoidosis [2].

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Discussion

Conclusion