Mendelian randomization analysis in three Japanese populations supports a causal role of alcohol consumption in lowering low-density lipid cholesterol levels and particle numbers
| Autor: | Masaki Sumi, Akira Fujiyoshi, Takashi Hisamatsu, Yasuharu Tabara, Katsuyuki Miura, Naoyuki Takashima, Maryam Zaid, Katsuhiko Kohara, Tetsuro Miki, Hirotsugu Ueshima |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male medicine.medical_specialty Alcohol Drinking Genotype Lipoproteins Alcohol 030204 cardiovascular system & hematology Biology Lipoprotein particle Cohort Studies 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Asian People Japan Internal medicine Cholesterylester transfer protein medicine Humans 030212 general & internal medicine Particle Size Ethanol metabolism Alleles Aged ALDH2 Genetics Cholesterol Aldehyde Dehydrogenase Mitochondrial Homozygote Mendelian Randomization Analysis Cholesterol LDL Middle Aged Atherosclerosis Cholesterol Ester Transfer Proteins Lipoproteins LDL Endocrinology chemistry biology.protein Female lipids (amino acids peptides and proteins) Lipoproteins HDL Cardiology and Cardiovascular Medicine Lipoprotein |
| Zdroj: | Atherosclerosis. 254:242-248 |
| ISSN: | 0021-9150 |
| Popis: | While alcohol consumption is known to increase plasma high-density lipoprotein (HDL) cholesterol levels, its relationship with low-density lipoprotein (LDL) cholesterol levels is unclear. Aldehyde dehydrogenase 2 (ALDH2) is a rate-controlling enzyme in alcohol metabolism, but a large number of Japanese people have the inactive allele. Here, we conducted a Mendelian randomization analysis using the ALDH2 genotype to clarify a causal role of alcohol on circulating cholesterol levels and lipoprotein particle numbers.This study was conducted in three independent general Japanese populations (men, n = 2289; women, n = 1940; mean age 63.3 ± 11.2 years). Alcohol consumption was assessed using a questionnaire. Lipoprotein particle numbers were determined by nuclear magnetic resonance spectroscopy.Alcohol consumption increased linearly in proportion to the number of subjects carrying the enzymatically active *1 allele in men (p 0.001). The *1 allele was also positively associated with HDL cholesterol level (adjusted mean ± standard error, *1*1: 60 ± 0.5, *1*2: 56 ± 0.6, *2*2: 55 ± 1.3 mg/dl, p 0.001) and inversely associated with LDL cholesterol level (116 ± 0.9, 124 ± 1.1, 130 ± 2.6 mg/dl, p 0.001). The *1 allele was also positively associated with HDL particle numbers (per-allele: 2.60 ± 0.32 μmol/l, p 0.001) and inversely associated with LDL particle numbers (-67.8 ± 19.6 nmol/l, p = 0.001). Additional Mendelian randomization analysis failed to clarify the involvement of cholesteryl ester transfer protein in alcohol-related changes in lipoprotein cholesterol levels. No significant association was observed in women, presumably due to their small amount of alcohol intake.Alcohol consumption has a causal role in not only increasing HDL cholesterol levels but also decreasing LDL cholesterol levels and particle numbers. |
| Databáze: | OpenAIRE |
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