Caspase 7 influences susceptibility to rheumatoid arthritis

Objective. The aim of this study was to investigate the possible role of the caspase 7 (CASP7) in susceptibility to rheumatoid arthritis (RA). Methods. Genotyping of three single nucleotide polymorphisms (SNPs) of the CASP7 gene: rs11593766 (G/T), rs2227310 (C/G) and rs2227309 (G/A) was performed in a total of 906 RA patients and 528 matched healthy controls using TaqMan assays. All the subjects were of Spanish Caucasian origin. A relative quantification of mRNA encoding the non-functional variant of procaspase 7 (isoform P) Vs functional isoforms was performed in total RNA from 32 healthy individuals using real-time PCR. Results. Only the rs2227309 SNP was found to be associated with susceptibility to RA. Frequency of the G allele was significantly higher among RA patients [overall frequency of the G allele 74.0% in cases vs 68.4% in controls, P=0.001, Odds ratio (OR)=1.32, 95% Confidence intervals (95% CI) 1.11-1.56] and a higher frequency of GG homozygous individuals was found in the RA patient group (overall frequency of GG genotype 56.0% in cases and 46.4% in controls, P=0.0005, OR= 1.47, 95%CI 1.18-1.83). A statistically significant deviation was observed to compare the relative expression of the procaspase 7 isoform beta in samples from individuals stratified according their rs2227309 genotypes (AA + AG: 1.36 0.55, n=19, vs GG: 2.35 t 0.74, n=13; P= 0.0002). Conclusion. Our results support involvement of the CASP7gene in the susceptibility to RA. The higher production of the no functional variant of CASP7 by individuals with a particular genotype could be the basis of this association.