title: CARD8 rs2043211 (p.C10X) polymorphism is not associated with disease susceptibility or cardiovascular events in Spanish rheumatoid arthritis patients.
abstract: Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis, which is the main cause of increased cardiovascular (CV) morbidity and mortality in RA patients. CARD8 is a constituent of inflammasome, which regulates interleukin 1-beta production, and has been associated with a worse disease course in early RA. One thousand six hundred twenty-one patients fulfilling the 1987 ACR classification criteria for RA and 1300 matched controls, were genotyped for the CARD8 rs2043211 (30T>A, p.C10X) single-nucleotide polymorphism (SNP) using predesigned TaqMan SNP genotyping assay. The genotyping success rate in our study was greater than 94%. We assessed CARD8 rs2043211 gene polymorphism results in 1530 Spanish RA patients in whom information on CV disease and CV risk factors was available at the time of the study. Also, a subgroup of patients with no history of CV events (n=276) was assessed for the potential influence of the rs2043211 variant in the development of subclinical atherosclerosis, by measurement of carotid intima-media thickness (IMT) and presence of carotid plaques. No statistically significant differences in allele or genotype frequencies for the rs2043211 CARD8 gene variant between patients with RA and controls were seen. Similarly, CARD8 rs2043211 (30T>A, p.C10X) SNP did not influence the development of CV events or the risk of CV events throughout the time. Likewise, no significant association between this gene variant and carotid IMT or the presence of plaques was found. In summary, our results do not support a role of the CARD8 rs2043211 gene variant in susceptibility to RA or in the development of CV disease in patients with RA.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: García-Bermúdez
authors.forename: Raquel
authors.initials: R
authors.lastname: López-Mejías
authors.forename: Carlos
authors.initials: C
authors.lastname: González-Juanatey
authors.forename: Alfonso
authors.initials: A
authors.lastname: Corrales
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ortiz
authors.forename: José A
authors.initials: JA
authors.lastname: Miranda-Filloy
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez-Vaquero
authors.forename: Benjamín
authors.initials: B
authors.lastname: Fernández-Gutiérrez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: Dora
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000235:genetics*; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000150:complications / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D018389:Codon, Nonsense; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013030:Spain
chemical_list: D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D018389:Codon, Nonsense; D009363:Neoplasm Proteins