Objectives: Copy number variants (CNVs) could explain a part of the missing heritability in rheumatoid arthritis (RA). Our goal is to investigate the association of RA with CNVs of three functional candidate genes, Glutathione S-transferase M1 (GSTM1), Glutathione S-transferase T1 (GSTT1) and Fcγ receptor type IIIAB (FCGR3B).
Methods: We quantified the absolute copy number of GSTM1, GSTT1 and FCGR3B genes using droplet digital PCR. Transmission of copy number alleles was investigated in trio families with RA using family-based association tests (Transmission Disequilibrium Test and Genotype Haplotype Relative Risk). Clinical, environmental and biological data on RA patients were also used to stratify patients sample in analysis.
Results: Copy numbers from zero to three were identified. Genotype combinations characterised in 182 trios allowed testing the association with RA. Genotypes without null allele of FCGR3B gene were significantly associated with RA (3.41x10-7). Three copy numbers of this gene is observed only in cases of RA (n=14) and a protective effect of null allele was characterised (OR=0.3 (0.17-0.53)).
Conclusions: CNVs in FCGR3B are associated with RA in our set of samples. This gene may play a role in physiopathology of this disease.