title: 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).
  
  
  CONCLUSIONS
  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.affiliation: Servicio de Inmunología, Hospital Universitario Virgen del Rocío, Avda Manuel Siurot s/n, 41013 Sevilla, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: García-Lozano
authors.forename: B
authors.initials: B
authors.lastname: Torres
authors.forename: O
authors.initials: O
authors.lastname: Fernández
authors.forename: G
authors.initials: G
authors.lastname: Orozco
authors.forename: A
authors.initials: A
authors.lastname: Alvarez-Márquez
authors.forename: A
authors.initials: A
authors.lastname: García
authors.forename: M A
authors.initials: MA
authors.lastname: González-Gay
authors.forename: A
authors.initials: A
authors.lastname: García
authors.forename: A
authors.initials: A
authors.lastname: Núñez-Roldán
authors.forename: J
authors.initials: J
authors.lastname: Martín
authors.forename: M F
authors.initials: MF
authors.lastname: González-Escribano
mesh_terms: D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D053179:Caspase 7 / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D053179:Caspase 7