title: Familial vs. sporadic sarcoidosis: BTNL2 polymorphisms, clinical presentations, and outcomes in a French cohort.
abstract: 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.
  
  
  
  The 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.
  
  
  
  Despite 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.
authors.affiliation: Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Université Claude Bernard - Lyon 1, EA-7426, Lyon, France. yves.pacheco@univ-lyon1.fr.|Université Claude Bernard Lyon 1 - EA-7426, 165 Chemin du Grand Revoyet, F-69495, Pierre Benite, France. yves.pacheco@univ-lyon1.fr.
authors.forename: Yves
authors.initials: Y
authors.lastname: Pacheco
authors.affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Plateforme de génétique moléculaire, CR-21076, Université Claude Bernard - Lyon 1, INSERM U1052, Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Calender
authors.affiliation: AP-HP, Hôpital Européen Georges Pompidou, Service de Pneumologie, Centre de Compétence des maladies pulmonaires rares, Université René Descartes - Paris 5, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Israël-Biet
authors.affiliation: Hospices Civils de Lyon, Service de Biostatistique, Université Claude Bernard - Lyon 1, CNRS UMR 5558, Lyon, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Roy
authors.affiliation: Hospices Civils de Lyon, Hôpital Lyon-Sud, Université Claude Bernard - Lyon1, INSERM U1052 - CNRS UMR5286, Lyon, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Lebecque
authors.affiliation: Hospices Civils de Lyon, Hôpital Louis Pradel, Université Claude Bernard - Lyon 1, UMR 754, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cottin
authors.affiliation: AP-HP, Hôpital Avicenne, Université Paris13, EA2363, COMUE Sorbonne Paris Cité, Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Bouvry
authors.affiliation: AP-HP, Hôpital Avicenne, Université Paris13, EA2363, COMUE Sorbonne Paris Cité, Paris, France.
authors.forename: Hilario
authors.initials: H
authors.lastname: Nunes
authors.affiliation: Hospices Civils de Lyon, Hôpital Croix-Rousse, Université Claude Bernard - Lyon 1, Lyon, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sève
authors.affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Université Claude Bernard - Lyon 1, Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pérard
authors.affiliation: Hospices Civils de Lyon, Hôpital Croix-Rousse, Université Claude Bernard - Lyon 1, Lyon, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Devouassoux
authors.affiliation: Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Université Claude Bernard - Lyon 1, EA-7426, Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Freymond
authors.affiliation: Hospices Civils de Lyon, Hôpital Louis Pradel, Université Claude Bernard - Lyon 1, UMR 754, Lyon, France.
authors.forename: Chahira
authors.initials: C
authors.lastname: Khouatra
authors.affiliation: Centre hospitalo-universitaire de Lille, Service de Pneumologie et Immunoallergologie, Centre de Compétence Maladies Pulmonaires Rares, Université Lille 2, Lille, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Wallaert
authors.affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Plateforme de génétique moléculaire, CR-21076, Université Claude Bernard - Lyon 1, INSERM U1052, Lyon, France.
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Lamy
authors.affiliation: Hospices Civils de Lyon, Service de Biostatistique, Université Claude Bernard - Lyon 1, CNRS UMR 5558, Lyon, France.
authors.forename: Mad-Hélénie
authors.initials: MH
authors.lastname: Elsensohn
authors.affiliation: Hospices Civils de Lyon, Service de Biostatistique, Université Claude Bernard - Lyon 1, CNRS UMR 5558, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Bardel
authors.affiliation: AP-HP, Hôpital Avicenne, Université Paris13, EA2363, COMUE Sorbonne Paris Cité, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
mesh_terms: D000328:Adult; D000071797:Butyrophilins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012507:Sarcoidosis / Q000235:genetics* / Q000473:pathology*
chemical_list: C408263:BTNL2 protein, human; D000071797:Butyrophilins
keywords: Candidate gene association study; Classification; Human BTNL2 protein; Medical genetics; Sarcoidosis