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Common genetic variation in MC4R does not affect atherosclerotic plaque phenotypes and cardiovascular disease outcomes

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  • Lisanne L Blauw
  • Raymond Noordam
  • Sander W van der Laan
  • Stella Trompet
  • Sander Kooijman
  • Diana van Heemst
  • Johan Wouter Jukema
  • Jessica van Setten
  • Gert J de Borst
  • Anne Tybjærg-Hansen
  • Gerard Pasterkamp
  • Jimmy F P Berbée
  • Patrick C N Rensen
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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.

Original languageEnglish
Article number932
JournalJournal of Clinical Medicine
Volume10
Issue number5
ISSN2077-0383
DOIs
Publication statusPublished - 1 Mar 2021

ID: 64827189