Open AccessC8orf13 – BLK is a genetic risk locus for systemic sclerosis and has additive effects with BANK1 : Results from a large french cohort and meta‐analysis
Author(s) -
Coustet Baptiste,
Dieudé Philippe,
Guedj Mickael,
Bouaziz Mathieu,
Avouac Jerome,
Ruiz Barbara,
Hachulla Eric,
Diot Elisabeth,
Cracowski JeanLuc,
Tiev Kiet,
Sibilia Jean,
Mouthon Luc,
Frances Camille,
Amoura Zahir,
Carpentier Patrick,
Cosnes Anne,
Meyer Olivier,
Kahan Andre,
Boileau Catherine,
Chiocchia Gilles,
Allanore Yannick
Publication year - 2011
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.30379
Subject(s) - genotype , odds ratio , locus (genetics) , allele , medicine , population , cohort , confidence interval , oncology , genetics , immunology , biology , gene , environmental health
Abstract Objective Accumulating evidence suggests that B cells are involved in systemic sclerosis (SSc). BANK1 has been reproducibly reported to be associated with diffuse cutaneous SSc (dcSSc). BLK encodes another B cell signal transducer, and a functional variant at the C8orf13 – BLK locus has been found to be associated with SSc in Caucasians. However, no independent replication has been reported, and there are discrepancies in the genotype–phenotype correlation between these studies in Caucasians and another study performed in the Japanese population. Therefore, in a large cohort of French Caucasians and using a meta‐analysis of the available data, this study was undertaken to determine whether the C8orf13 – BLK locus is associated with SSc, and to assess the possibility of interaction between BLK and BANK1 in SSc. Methods The C8orf13 – BLK rs13277113 genotype was determined in 1,031 patients with SSc and 1,014 control subjects for whom BANK1 genotypes were available. Meta‐analysis of the 3 available data sets (6,078 individuals) was also performed. Results Minor allele frequencies for rs13277113 revealed an association restricted to the dcSSc subtype ( P = 0.012, odds ratio [OR] 1.29) in the French sample. Meta‐analysis of the combined Caucasian populations showed an association of this genotype with both SSc ( P = 0.0013, OR 1.16, 95% confidence interval [95% CI] 1.06–1.26) and dcSSc ( P = 0.0012, OR 1.23, 95% CI 1.08–1.39). Inclusion of the Japanese population confirmed the overall association with the disease, with the strongest association observed with dcSSc ( P = 3.27 × 10 −5 , OR 1.27). Secondary analysis in the French sample revealed additive effects between C8orf13 – BLK and BANK1, mainly in the dcSSc subset. Conclusion These results confirm C8orf13 – BLK as an SSc risk locus. The strongest effects, and particularly additive effects, were observed in the interaction between C8orf13 – BLK and BANK1 in the dcSSc subset.