title: Protective Role of the Interleukin 33 rs3939286 Gene Polymorphism in the Development of Subclinical Atherosclerosis in Rheumatoid Arthritis Patients.
abstract: OBJECTIVE
  To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US).
  
  
  RESULTS
  RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed.
  
  
  CONCLUSIONS
  In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA.
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: López-Mejías
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Genre
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Remuzgo-Martínez
authors.affiliation: Rheumatology Department, Hospital Universitario Doctor Peset, Valencia, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Robustillo-Villarino
authors.affiliation: Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC, Granada, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: García-Bermúdez
authors.affiliation: Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IDIVAL, Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Corrales
authors.affiliation: Cardiology Department, Hospital Lucus Augusti, Lugo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: González-Juanatey
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Ubilla
authors.affiliation: Rheumatology Department, Hospital Lucus Augusti, Lugo, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Miranda-Filloy
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Mijares
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain.
authors.forename: Trinitario
authors.initials: T
authors.lastname: Pina
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Rheumatology Department, Hospital Universitario Doctor Peset, Valencia, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Alegre-Sancho
authors.affiliation: Rheumatology Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Ramírez Huaranga
authors.affiliation: Rheumatology Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
authors.forename: María D
authors.initials: MD
authors.lastname: Mínguez Sánchez
authors.affiliation: Rheumatology Department, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Tejera Segura
authors.affiliation: Rheumatology Department, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Ferraz-Amaro
authors.affiliation: Rheumatology Department, Hospital Universitario la Princesa, IIS-Princesa, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Vicente
authors.affiliation: Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC, Granada, Spain.
authors.forename: F David
authors.initials: FD
authors.lastname: Carmona
authors.affiliation: Rheumatology Department, Hospital Universitario la Princesa, IIS-Princesa, Madrid, Spain.
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.affiliation: Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC, Granada, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain.|Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Health Research Institute of Santiago de Compostela (IDIS), Division of Rheumatology, Clinical University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000235:genetics*; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics*; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D000067596:Interleukin-33 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics; D012306:Risk; D014463:Ultrasonography
chemical_list: C508590:IL1R1 protein, human; D000067596:Interleukin-33; D053573:Receptors, Interleukin-1 Type I