PT  - JOURNAL ARTICLE
AU  - Katherine P Liao
AU  - Dorothée Diogo
AU  - Jing Cui
AU  - Tianxi Cai
AU  - Yukinori Okada
AU  - Vivian S Gainer
AU  - Shawn N Murphy
AU  - Namrata Gupta
AU  - Daniel Mirel
AU  - Ashwin N Ananthakrishnan
AU  - Peter Szolovits
AU  - Stanley Y Shaw
AU  - Soumya Raychaudhuri
AU  - Susanne Churchill
AU  - Isaac Kohane
AU  - Elizabeth W Karlson
AU  - Robert M Plenge
TI  - Association between low density lipoprotein and rheumatoid arthritis genetic factors with low density lipoprotein levels in rheumatoid arthritis and non-rheumatoid arthritis controls
AID  - 10.1136/annrheumdis-2012-203202
DP  - 2014 Jun 01
TA  - Annals of the Rheumatic Diseases
PG  - 1170--1175
VI  - 73
IP  - 6
4099  - http://ard.bmj.com/content/73/6/1170.short
4100  - http://ard.bmj.com/content/73/6/1170.full
SO  - Ann Rheum Dis2014 Jun 01; 73
AB  - Objectives 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.