Common genetic variation in mc4r does not affect atherosclerotic plaque phenotypes and cardiovascular disease outcomes
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Common genetic variation in mc4r does not affect atherosclerotic plaque phenotypes and cardiovascular disease outcomes. / Blauw, Lisanne L.; Noordam, Raymond; van der Laan, Sander W.; Trompet, Stella; Kooijman, Sander; van Heemst, Diana; Jukema, Johan Wouter; van Setten, Jessica; de Borst, Gert J.; Tybjærg-Hansen, Anne; Pasterkamp, Gerard; Berbée, Jimmy F.P.; Rensen, Patrick C.N.
I: Journal of Clinical Medicine, Bind 10, Nr. 5, 932, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Common genetic variation in mc4r does not affect atherosclerotic plaque phenotypes and cardiovascular disease outcomes
AU - Blauw, Lisanne L.
AU - Noordam, Raymond
AU - van der Laan, Sander W.
AU - Trompet, Stella
AU - Kooijman, Sander
AU - van Heemst, Diana
AU - Jukema, Johan Wouter
AU - van Setten, Jessica
AU - de Borst, Gert J.
AU - Tybjærg-Hansen, Anne
AU - Pasterkamp, Gerard
AU - Berbée, Jimmy F.P.
AU - Rensen, Patrick C.N.
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - BMI
KW - Cardiovascular disease
KW - Genetics
KW - MC4R
U2 - 10.3390/jcm10050932
DO - 10.3390/jcm10050932
M3 - Journal article
C2 - 33804309
AN - SCOPUS:85114071439
VL - 10
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
SN - 2077-0383
IS - 5
M1 - 932
ER -
ID: 279821054