Abstract

We analyzed the effects of the common BMI-increasing melanocortin 4 receptor (MC4R) rs17782313-C allele with a minor allele frequency of 0.22-0.25 on (1) cardiovascular disease outcomes in two large population-based cohorts (Copenhagen City Heart Study and Copenhagen General Population Study, n = 106,018; and UK Biobank, n = 357,426) and additionally in an elderly population at risk for cardiovascular disease (n = 5241), and on (2) atherosclerotic plaque phenotypes in samples of patients who underwent endarterectomy (n = 1439). Using regression models, we additionally analyzed whether potential associations were modified by sex or explained by changes in body mass index. We confirmed the BMI-increasing effects of +0.22 kg/m2 per additional copy of the C allele (p < 0.001). However, we found no evidence for an association of common MC4R genetic variation with coronary artery disease (HR 1.03; 95% CI 0.99, 1.07), ischemic vascular disease (HR 1.00; 95% CI 0.98, 1.03), myocardial infarction (HR 1.01; 95% CI 0.94, 1.08 and 1.02; 0.98, 1.07) or stroke (HR 0.93; 95% CI 0.85, 1.01), nor with any atherosclerotic plaque phenotype. Thus, common MC4R genetic variation, despite increasing BMI, does not affect cardiovascular disease risk in the general population or in populations at risk for cardiovascular disease.

Overview publication

TitleCommon Genetic Variation in MC4R Does Not Affect Atherosclerotic Plaque Phenotypes and Cardiovascular Disease Outcomes.
DateMarch 1st, 2021
Issue nameJournal of clinical medicine
Issue numberv10.5
DOI10.3390/jcm10050932
PubMed33804309
AuthorsBlauw LL, Noordam R, van der Laan SW, Trompet S, Kooijman S, van Heemst D, Jukema JW, van Setten J, de Borst GJ, Tybjærg-Hansen A, Pasterkamp G, Berbée JFP & Rensen PCN
KeywordsBMI, MC4R, atherosclerosis, cardiovascular disease, genetics
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