Caspase 7 influences susceptibility to rheumatoid arthritis.

Abstract

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 beta) 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 +/- 0.74, n = 13; P = 0.0002).

CONCLUSION:

Our results support involvement of the CASP7 gene 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.

• Authors: J R García-Lozano, B Torres, O Fernández, G Orozco, A Alvarez-Márquez, A García, M A González-Gay, A García, A Núñez-Roldán, J Martín, M F González-Escribano
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 46 Issue 8 Pg. 1243-7 (Aug 2007) ISSN: 1462-0324 [Print] England
• PMID: 17504820 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Caspase 7

Topics

• Arthritis, Rheumatoid (enzymology, genetics)
• Base Sequence
• Case-Control Studies
• Caspase 7 (genetics, metabolism)
• Cohort Studies
• Gene Expression
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• Haplotypes
• Humans
• Molecular Sequence Data
• Polymorphism, Single Nucleotide
• RNA, Messenger (genetics)