C8orf13-BLK Is a Genetic Risk Locus for Systemic Sclerosis and Has Additive Effects With BANK1: Results From a Large French Cohort and Meta-Analysis

INSERM U1016, Université Paris Descartes, Paris, France.
Arthritis & Rheumatology (Impact Factor: 7.76). 07/2011; 63(7):2091-6. DOI: 10.1002/art.30379
Source: PubMed


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.
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.
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.
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.

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Available from: Philippe Dieudé, Feb 20, 2014
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    • "In a subsequent analysis, they added an NLRP1 polymorphism to the list of variants interacting with STAT4 and IRF5 [34]. In contrast, the SSc-associated BLK region had an additive effect with BANK1 in the dcSSc subset [53]. An American study showed that the STAT4 polymorphism was predominantly enriched in SSc patients who carried the CC genotype at TBX21 rs11650354 [16]. "
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