Associations of HLA-DRB1 shared epitope alleles with cardiovascular disease and events in a multi-ethnic community-living population: The multi-ethnic study of atherosclerosis (MESA).

Objective: Rheumatoid arthritis (RA) has been considered an independent risk factor for cardiovascular disease (CVD), where RA and CVD later manifest following genetic predisposition and an extended preclinical phase.TheHLA-DRB1Shared Epitope (SE)allelespredispose for RA andare associated withhigherrisk of CV mortality in RA patients, but have not been evaluated in a community-living population.Thus, we evaluated whetherHLA-DRB1 (SE) alleleswereassociated with subclinical CVD, CV events, and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: We performed HLA typing in 955 MESA participants and evaluated associations of SE alleles with coronary artery calcium (CAC) and abdominal aortic calcium (AAC); risk difference for CAC, AAC severity, and carotid intima media thickness (cIMT); and associations of SE with all-cause mortality, CVD and non-CVD death, and CV events.

Results: Among 955 participants, 30 % were HLA-DRB1 SE positive. SE positivity was not significantly associated with higher risk of CAC, AAC, cIMT, CV events, or mortality. DRB1*10:01 demonstrated 2.63-fold higher risk for CAC (95 % CI 1.17-5.99); DRB1*14:02 demonstrated 42 % higher risk for AAC (95 % CI 1.17-1.74); and DRB1*04:05 demonstrated 24 % lower risk for AAC (95 % CI 0.58-0.99).

Conclusion: In a multi-ethnic community-living population, HLA-DRB1 SE alleles were not associated with subclinical CVD, CV events, or mortality. However, individual allele-associations with subclinical CVD suggested variability in risk.