title: Association of polymorphisms modulating low-density lipoprotein cholesterol with susceptibility, severity, and progression of rheumatoid arthritis.
abstract: OBJECTIVE
  Dyslipidemia, a risk factor for cardiovascular diseases, is more prevalent in patients with rheumatoid arthritis (RA) than in the general population. We investigated whether single-nucleotide polymorphisms (SNP) modulating low-density lipoprotein (LDL) cholesterol affect susceptibility, severity, and progression of RA.
  
  
  METHODS
  We enrolled 302 patients with RA and 1636 healthy controls, and investigated the SNP modulating LDL cholesterol. Clinical characteristics of RA, serum adipocytokine concentrations, and radiographic severity were analyzed according to genotype score based on the number of unfavorable alleles. The influence of genotype score on radiographic progression was also investigated using multivariable logistic models.
  
  
  RESULTS
  We identified 3 SNP (rs688, rs693, and rs4420638) modulating LDL cholesterol in Koreans, which correlated well with LDL cholesterol levels in both patients with RA and controls. Among them, 2 SNP, rs688 and rs4420638, were more prevalent in patients with RA than in controls. In patients with RA carrying more unfavorable alleles (genotype score ≥ 3), disease activity measures, serum adipocytokine levels, and radiographic severity were all increased. The genotype score was an independent risk factor for radiographic progression of RA over 2 years, and its effect was greater than the influence of conventional risk factors.
  
  
  CONCLUSIONS
  SNP modulating LDL cholesterol influence the risk, activity, and severity of RA. These results provide the first evidence that genetic mechanisms linked to dyslipidemia may directly contribute to the susceptibility and prognosis of RA, a representative of chronic inflammatory diseases, explaining the high incidence of dyslipidemia in RA.
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea, School of Medicine, and the Research Institute of Immunobiology, The Catholic University of Korea, Gyeonggi-do, Korea.
authors.forename: Yune-Jung
authors.initials: YJ
authors.lastname: Park
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Yoo
authors.forename: Susanna
authors.initials: S
authors.lastname: Choi
authors.forename: Hee-Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Ho-Sung
authors.initials: HS
authors.lastname: Yoon
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Cho
authors.forename: Ki-Dong
authors.initials: KD
authors.lastname: Yoo
authors.forename: Wan-Uk
authors.initials: WU
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics*; D018450:Disease Progression; D050171:Dyslipidemias / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011859:Radiography; D056910:Republic of Korea; D012720:Severity of Illness Index
chemical_list: D008078:Cholesterol, LDL
keywords: DYSLIPIDEMIA; POLYMORPHISMS; RADIOGRAPHIC PROGRESSION; RHEUMATOID ARTHRITIS