title: Lack of association between TLR4 rs4986790 polymorphism and risk of cardiovascular disease in patients with rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Toll-like receptor-4 (TLR4) activates the innate immune response via NF-kB pathway and mitogen-activated protein kinase signaling, leading to expression of proinflammatory cytokines and chemokines. The G allele of TLR4 rs4986790 (+896A>G, Asp299Gly) gene polymorphism has been implicated in reduction of risk of atherosclerosis. In this study, 1481 RA patients fulfilling the 1987 American College of Rheumatology (ACR) criteria were genotyped for the rs4986790 TLR4 variant to determine the influence of this variant in the risk of CV events in these patients. Also, HLA-DRB1 status was determined using molecular based methods. Moreover, potential influence of rs4986790 variant in the development of subclinical atherosclerosis was assessed in a subgroup of RA patients with no history of CV events by the measurement of surrogate markers of subclinical atherosclerosis. No statistically significant differences in allele or genotype frequencies for the rs4986790 variant between RA patients who experienced CV events or not were found. Likewise, no significant association between this gene variant and any of the surrogate markers of subclinical atherosclerosis was found. In summary, results in our study do not support the hypothesis that the rs4986790 (+896A>G, Asp299Gly) TLR4 variant may influence predisposition for subclinical atherosclerosis and clinically evident CV disease in RA patients.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-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: Santos
authors.initials: S
authors.lastname: Castañeda
authors.forename: José A
authors.initials: JA
authors.lastname: Miranda-Filloy
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.forename: Benjamín
authors.initials: B
authors.lastname: Fernández-Gutiérrez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: Isidoro
authors.initials: I
authors.lastname: González-Alvaro
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez-Vaquero
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; D001172:Arthritis, Rheumatoid / Q000150:complications*; D050197:Atherosclerosis / Q000235:genetics; D002318:Cardiovascular Diseases / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4