Mendelian randomization analysis of cholesteryl ester transfer protein and subclinical atherosclerosis: A population-based study

Autor: Christen, T., Trompet, S., Noordam, R., Blauw, L.L., Gast, K.B., Rensen, P.C.N., Dijk, K.W. van, Rosendaal, F.R., Mutsert, R. de, Jukema, W., NEO Study
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Epidemiology
Endocrinology
Diabetes and Metabolism
030204 cardiovascular system & hematology
Carotid Intima-Media Thickness
Body Mass Index
Cohort Studies
chemistry.chemical_compound
0302 clinical medicine
Anacetrapib
Risk Factors
Medicine
Ultrasonography
education.field_of_study
Nutrition and Dietetics
Framingham Risk Score
biology
Cohort
Mendelian Randomization Analysis
Middle Aged
Cholesterol
lipids (amino acids
peptides
and proteins)
Female
Cardiology and Cardiovascular Medicine
Cohort study
Adult
medicine.medical_specialty
Genotype
Population
Polymorphism
Single Nucleotide
03 medical and health sciences
Internal medicine
Cholesterylester transfer protein
Mendelian randomization
Internal Medicine
Humans
education
Alleles
Triglycerides
Aged
business.industry
Atherosclerosis
Cholesterol Ester Transfer Proteins
030104 developmental biology
Endocrinology
Reverse cholesterol transport
chemistry
biology.protein
business
Body mass index
Zdroj: Journal of Clinical Lipidology, 12(1), 137-144
Journal of Clinical Lipidology
Popis: Background Several trials to prevent cardiovascular disease by inhibiting cholesteryl ester transfer protein (CETP) have failed, except Randomized EValuation of the Effects of Anacetrapib through Lipid-modification. Thus far, it is unclear to what extent CETP is causally related to measures of atherosclerosis. Objective The aim of the article was to study the causal relationship between genetically determined CETP concentration and carotid intima-media thickness (cIMT) in a population-based cohort study. Methods In the Netherlands Epidemiology of Obesity study, participants were genotyped, and cIMT was measured by ultrasonography. We examined the relation between a weighted genetic risk score for CETP concentration, based on 3 single-nucleotide polymorphisms that have previously been shown to largely determine CETP concentration and cIMT using Mendelian randomization in the total population and in strata by sex, Framingham 10-year risk, (pre)diabetes, high-density lipoprotein cholesterol, triglycerides, and statin use. Results We analyzed 5655 participants (56% women) with a mean age of 56 (range 44–66) years, body mass index of 26 (range 17–61) kg/m 2 , and serum CETP of 2.47 (range 0.68–5.33) μg/mL. There was no evidence for a causal relation between genetically determined CETP and cIMT in the total population, but associations were differently directed in men (16 μm per μg/mL increase in genetically determined CETP; 95% confidence interval: −8, 39) and women (−8 μm; −25, 9). Genetically determined CETP appeared to be associated with cIMT in normoglycemic men (26 μm; −1, 52) and in (pre)diabetic women (48 μm; −2, 98). Conclusion In this population-based study, there was no causal relation between genetically determined CETP concentration and cIMT in the total population although we observed directionally differing effects in men and women. Stratified results suggested associations in individuals with different cardiometabolic risk factor profiles, which require replication.
Databáze: OpenAIRE
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