Background/Purpose: Human leukocyte antigen (HLA) DRB1 alleles with specific common amino acids referred to as “the shared epitope (SE)”, have been linked to cardiovascular mortality in inflammatory polyarthritis. Thesehaplotypes associate with ST-elevation myocardial infarction in the general population. However, less is known about the HLA-DRB1 alleles with other cardiovascular (CV) events. We aimed to determine associations of the HLA-DRB1 SE alleles (04:04, 04:05, 04:01, 04:08, 01:01, 14:02, 10:01, 03:01, 03:02) with ischemic events and mortality in a multi-ethnic community-living population.

Methods: Within the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study designed to determine risk factors and progression of subclinical and clinical CVD, a subset of 955 participants who completed the Abdominal Aortic Calcium Ancillary Study and had complete measures of HLA typing and cardiac imaging were evaluated. We defined shared epitope positive [SE(+)] as being positive for any of the HLA-DRB1 SE alleles; and evaluated associations of SE positivity with all-cause mortality, CVD death (defined as secondary to stroke, coronary heart disease, other atherosclerotic death, or other CVD death), non-CVD death, angina, and myocardial infarction (MI) using Cox proportional hazards models. The covariates in our fully adjusted analysis included age, sex, race/ethnicity, diabetes mellitus, systolic blood pressure, current smoking, ever having cancer, eGFR, current use of anti-hypertensive medications, nonsteroidal anti-inflammatory drugs, and IL-6.

Results: Among the 955 MESA participants, 46% were positive for the shared epitope—38% carried a single allele, and 8% carried two alleles. Average age was 60±9, 47% were women, 51% were White, 9% were Asian, 16% were Black, and 24% were Hispanic/Latino. Age, sex, blood pressure, cholesterol, and inflammatory markers (CRP, TNF-α, IL 6) were similar between the SE(+) and SE(-) participants, but racial distributions differed where SE(+) had a higher proportion of white (51% vs 38%) and lower proportion of Asian (9% vs 17%) and Black (16% vs 21%) participants compared to SE(-). Both SE (+) and (-) had 24% Hispanic/ Latino. Being positive for the SE was not significantly associated with a higher risk of all-cause mortality, CVD death, non-CVD death, angina, or MI compared to those who were SE negative. The mean follow-up time was 15.3 ± 0.9 years.

Conclusion: HLA-DRB1 SE alleles were not associated with a higher risk of ischemic events or mortality in a multi-ethnic community-living population.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-hla-drb1-alleles-with-ischemic-events-and-mortality-in-a-multi-ethnic-community-living-population/