title: Association study of MIA3 rs17465637 polymorphism with cardiovascular disease in rheumatoid arthritis patients.
abstract: Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis. Melanoma inhibitor protein 3 (MIA3) is required for the export of collagen VlI (COL7A1) from the endoplasmic reticulum and it appears to be a tumor suppressor of malignant melanoma. Genome-wide association studies have described an association between MIA3 rs17465637 A/C polymorphisms and coronary artery disease and myocardial infarction. Because of that, we assessed the MIA3 rs17465637 polymorphism in 1505 RA Spanish patients stratified according to the presence/absence of cardiovascular (CV) disease. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using carotid ultrasound to establish carotid intima-media wall thickness and carotid plaques and brachial ultrasonography to determine the presence of endothelial dysfunction by flow-mediated endothelium-dependent and independent vasodilatation. MIA3 rs17465637 allele A showed a trend for association with the presence of carotid plaques (odds ratio 1.56, 95% confidence interval [0.96-2.51]; p=0.07). However, apart from an association of the MIA3 rs17465637 A allele with the risk of CV events in RA patients with dyslipidemia (p=0.018), no other significant associations were found between the presence of MIA3 rs17465637 A allele and the risk of suffering CV events or other surrogate markers of atherosclerosis. In conclusion, our results suggest a potential association of the MIA3 rs17465637 with CV disease in dyslipidemic patients with RA. However, additional studies are required to better establish the role of the MIA3 gene in mechanisms leading to the accelerated atherogenesis observed in RA.
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: Alfonso
authors.initials: A
authors.lastname: Corrales
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
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: Isidoro
authors.initials: I
authors.lastname: González-Álvaro
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 / Q000235:genetics*; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: C497396:ARNT protein, human; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator