title: Association between low density lipoprotein and rheumatoid arthritis genetic factors with low density lipoprotein levels in rheumatoid arthritis and non-rheumatoid arthritis controls.
abstract: OBJECTIVE
  While genetic determinants of low density lipoprotein (LDL) cholesterol levels are well characterised in the general population, they are understudied in rheumatoid arthritis (RA). Our objective was to determine the association of established LDL and RA genetic alleles with LDL levels in RA cases compared with non-RA controls.
  
  
  METHODS
  Using data from electronic medical records, we linked validated RA cases and non-RA controls to discarded blood samples. For each individual, we extracted data on: first LDL measurement, age, gender and year of LDL measurement. We genotyped subjects for 11 LDL and 44 non-HLA RA alleles, and calculated RA and LDL genetic risk scores (GRS). We tested the association between each GRS and LDL level using multivariate linear regression models adjusted for age, gender, year of LDL measurement and RA status.
  
  
  RESULTS
  Among 567 RA cases and 979 controls, 80% were female and mean age at the first LDL measurement was 55 years. RA cases had significantly lower mean LDL levels than controls (117.2 vs 125.6 mg/dl, respectively, p<0.0001). Each unit increase in LDL GRS was associated with 0.8 mg/dl higher LDL levels in both RA cases and controls (p=3.0×10(-7)). Each unit increase in RA GRS was associated with 4.3 mg/dl lower LDL levels in both groups (p=0.01).
  
  
  CONCLUSIONS
  LDL alleles were associated with higher LDL levels in RA. RA alleles were associated with lower LDL levels in both RA cases and controls. As RA cases carry more RA alleles, these findings suggest a genetic basis for epidemiological observations of lower LDL levels in RA.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, , Boston, Massachusetts, USA.
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Liao
authors.forename: Dorothée
authors.initials: D
authors.lastname: Diogo
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.forename: Tianxi
authors.initials: T
authors.lastname: Cai
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Okada
authors.forename: Vivian S
authors.initials: VS
authors.lastname: Gainer
authors.forename: Shawn N
authors.initials: SN
authors.lastname: Murphy
authors.forename: Namrata
authors.initials: N
authors.lastname: Gupta
authors.forename: Daniel
authors.initials: D
authors.lastname: Mirel
authors.forename: Ashwin N
authors.initials: AN
authors.lastname: Ananthakrishnan
authors.forename: Peter
authors.initials: P
authors.lastname: Szolovits
authors.forename: Stanley Y
authors.initials: SY
authors.lastname: Shaw
authors.forename: Soumya
authors.initials: S
authors.lastname: Raychaudhuri
authors.forename: Susanne
authors.initials: S
authors.lastname: Churchill
authors.forename: Isaac
authors.initials: I
authors.lastname: Kohane
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Plenge
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D008077:Lipoproteins, LDL
keywords: Gene Polymorphism; Lipids; Rheumatoid Arthritis