Mendelian randomization analysis in three Japanese populations supports a causal role of alcohol consumption in lowering low-density lipid cholesterol levels and particle numbers

被引:26
作者
Tabara, Yasuharu [1 ,2 ]
Ueshima, Hirotsugu [3 ,4 ]
Takashima, Naoyuki [3 ]
Hisamatsu, Takashi [3 ,4 ]
Fujiyoshi, Akira [3 ]
Zaid, Maryam [3 ]
Sumi, Masaki [3 ]
Kohara, Katsuhiko [5 ]
Miki, Tetsuro [1 ,2 ]
Miura, Katsuyuki [3 ,4 ]
机构
[1] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Sakyo Ku, Shogoinkawara Cho 53, Kyoto 6068507, Japan
[2] Ehime Univ, Grad Sch Med, Dept Geriatr Med, Toon City, Ehime 7910295, Japan
[3] Shiga Univ Med Sci, Dept Publ Hlth, Seta Tsukinowa Cho, Otsu, Shiga 5202192, Japan
[4] Shiga Univ Med Sci, Ctr Epidemiol Res Asia, Seta Tsukinowa Cho, Otsu, Shiga 5202192, Japan
[5] Ehime Univ, Fac Collaborat Reg Innovat, Dept Reg Resource Management, Matsuyama, Ehime 7908577, Japan
基金
美国国家卫生研究院;
关键词
Alcohol consumption; Aldehyde dehydrogenase 2; LDL cholesterol; LDL particles; Genotype; Mendelian randomization analysis; CARDIOVASCULAR RISK-FACTORS; CORONARY-HEART-DISEASE; BLOOD-PRESSURE; SUBCLINICAL ATHEROSCLEROSIS; DEHYDROGENASE GENOTYPES; ARTERIAL STIFFNESS; ASSOCIATION; LIPOPROTEIN; MEN; METAANALYSIS;
D O I
10.1016/j.atherosclerosis.2016.08.021
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and aims: 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. Methods: 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. Results: 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 mmol/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. Conclusions: Alcohol consumption has a causal role in not only increasing HDL cholesterol levels but also decreasing LDL cholesterol levels and particle numbers. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:242 / 248
页数:7
相关论文
共 43 条
[1]   A Mendelian randomization study of the effect of type-2 diabetes on coronary heart disease [J].
Ahmad, Omar S. ;
Morris, John A. ;
Mujammami, Muhammad ;
Forgetta, Vincenzo ;
Leong, Aaron ;
Li, Rui ;
Turgeon, Maxime ;
Greenwood, Celia M. T. ;
Thanassoulis, George ;
Meigs, James B. ;
Sladek, Robert ;
Richards, J. Brent .
NATURE COMMUNICATIONS, 2015, 6
[2]   The inherent accuracy of 1H NMR spectroscopy to quantify plasma lipoproteins is subclass dependent [J].
Ala-Korpela, Mika ;
Lankinen, Niko ;
Salminen, Aino ;
Suna, Teemu ;
Soininen, Pasi ;
Laatikainen, Reino ;
Ingman, Petri ;
Jauhiainen, Matti ;
Taskinen, Marja-Riitta ;
Heberger, Karoly ;
Kaski, Kimmo .
ATHEROSCLEROSIS, 2007, 190 (02) :352-358
[3]  
Amamoto K, 2002, HYPERTENS RES, V25, P857
[4]   Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1 [J].
Beulens, JWJ ;
Sierksma, A ;
van Tol, A ;
Fournier, N ;
van Gent, T ;
Paul, JL ;
Hendriks, HFJ .
JOURNAL OF LIPID RESEARCH, 2004, 45 (09) :1716-1723
[5]   Mendelian randomization studies: a review of the approaches used and the quality of reporting [J].
Boef, Anna G. C. ;
Dekkers, Olaf M. ;
le Cessie, Saskia .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2015, 44 (02) :496-511
[6]   Effects of ethanol intake on lipoproteins and atherosclerosis [J].
Brinton, Eliot A. .
CURRENT OPINION IN LIPIDOLOGY, 2010, 21 (04) :346-351
[7]   Alcohol intake and cardiovascular risk factors: A Mendelian randomisation study [J].
Cho, Yoonsu ;
Shin, So-Youn ;
Won, Sungho ;
Relton, Caroline L. ;
Smith, George Davey ;
Shin, Min-Jeong .
SCIENTIFIC REPORTS, 2015, 5
[8]   ALCOHOL INTAKE AND SERUM-LIPIDS IN A JAPANESE POPULATION [J].
CHOUDHURY, SR ;
UESHIMA, H ;
KITA, Y ;
KOBAYASHI, KM ;
OKAYAMA, A ;
YAMAKAWA, M ;
HIRAO, Y ;
ISHIKAWA, M ;
MIYOSHI, Y .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 1994, 23 (05) :940-947
[9]   ALCOHOL INTAKE IN RELATION TO DIET AND OBESITY IN WOMEN AND MEN [J].
COLDITZ, GA ;
GIOVANNUCCI, E ;
RIMM, EB ;
STAMPFER, MJ ;
ROSNER, B ;
SPEIZER, FE ;
GORDIS, E ;
WILLETT, WC .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1991, 54 (01) :49-55
[10]   Alcohol dosing and total mortality in men and women - An updated meta-analysis of 34 prospective studies [J].
Di Castelnuovo, Augusto ;
Costanzo, Simona ;
Bagnardi, Vincenzo ;
Donati, Maria Benedetta ;
Iacoviello, Licia ;
de Gaetano, Giovanni .
ARCHIVES OF INTERNAL MEDICINE, 2006, 166 (22) :2437-2445