Genetic and expression analysis of CASP7 gene in a European Caucasian population with rheumatoid arthritis.

OBJECTIVE: To study the possible role of the caspase 7 (CASP7) gene in susceptibility to rheumatoid arthritis (RA) in a European Caucasian population.
METHODS: CASP7 rs2227309 single nucleotide polymorphism (SNP) was genotyped in 197 French RA trio families and in 252 European RA families available for replication using Taqman allelic discrimination assay. Relative quantification of caspase 7 isoforms alpha and beta mRNA expression was performed from whole blood in 25 unrelated patients with RA and in 15 healthy controls by real-time quantitative reverse transcription-polymerase chain reaction. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies, the transmission disequilibrium test, and the genotype relative risk.
RESULTS: We observed, in the first sample, a significant association of rs2227309-AA genotype with RA [p=0.03, odds ratio (OR) 2.11 (95% CI 1.0-4.6)]. The second sample did not show any significant association of the AA genotype with RA [p=0.6, OR 0.87 (95% CI 0.4-1.8)]. When the 2 samples were combined, no significant association of the AA genotype [p=0.3, OR 1.32 (95% CI 0.8-2.2)] was observed. CASP7 isoforms alpha and beta mRNA were expressed in patients with RA at lower level than in healthy controls (-89%, p=0.003 and -47%, p=0.01; respectively).
CONCLUSION: CASP7 rs2227309 SNP was not associated with RA in a European Caucasian population. Nevertheless, CASP7 isoforms alpha and beta could have an involvement in the apoptosis process in RA.