Yasuharu Tabara1, Hirotsugu Ueshima2, Naoyuki Takashima3, Takashi Hisamatsu2, Akira Fujiyoshi3, Maryam Zaid3, Masaki Sumi3, Katsuhiko Kohara4, Tetsuro Miki5, Katsuyuki Miura2. 1. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan; Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon City, Ehime 791-0295, Japan. Electronic address: tabara@genome.med.kyoto-u.ac.jp. 2. Department of Public Health, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan; Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan. 3. Department of Public Health, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan. 4. Department of Regional Resource Management, Faculty of Collaborative Regional Innovation, Ehime University, Matsuyama, Ehime 790-8577, Japan. 5. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan; Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon City, Ehime 791-0295, Japan.
Abstract
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 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. CONCLUSIONS: Alcohol consumption has a causal role in not only increasing HDL cholesterol levels but also decreasing LDL cholesterol levels and particle numbers.
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 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. CONCLUSIONS:Alcohol consumption has a causal role in not only increasing HDL cholesterol levels but also decreasing LDL cholesterol levels and particle numbers.
Authors: Paul S de Vries; Michael R Brown; Amy R Bentley; Yun J Sung; Thomas W Winkler; Ioanna Ntalla; Karen Schwander; Aldi T Kraja; Xiuqing Guo; Nora Franceschini; Ching-Yu Cheng; Xueling Sim; Dina Vojinovic; Jennifer E Huffman; Solomon K Musani; Changwei Li; Mary F Feitosa; Melissa A Richard; Raymond Noordam; Hugues Aschard; Traci M Bartz; Lawrence F Bielak; Xuan Deng; Rajkumar Dorajoo; Kurt K Lohman; Alisa K Manning; Tuomo Rankinen; Albert V Smith; Salman M Tajuddin; Evangelos Evangelou; Mariaelisa Graff; Maris Alver; Mathilde Boissel; Jin Fang Chai; Xu Chen; Jasmin Divers; Ilaria Gandin; Chuan Gao; Anuj Goel; Yanick Hagemeijer; Sarah E Harris; Fernando P Hartwig; Meian He; Andrea R V R Horimoto; Fang-Chi Hsu; Anne U Jackson; Anuradhani Kasturiratne; Pirjo Komulainen; Brigitte Kühnel; Federica Laguzzi; Joseph H Lee; Jian'an Luan; Leo-Pekka Lyytikäinen; Nana Matoba; Ilja M Nolte; Maik Pietzner; Muhammad Riaz; M Abdullah Said; Robert A Scott; Tamar Sofer; Alena Stančáková; Fumihiko Takeuchi; Bamidele O Tayo; Peter J van der Most; Tibor V Varga; Yajuan Wang; Erin B Ware; Wanqing Wen; Lisa R Yanek; Weihua Zhang; Jing Hua Zhao; Saima Afaq; Najaf Amin; Marzyeh Amini; Dan E Arking; Tin Aung; Christie Ballantyne; Eric Boerwinkle; Ulrich Broeckel; Archie Campbell; Mickaël Canouil; Sabanayagam Charumathi; Yii-Der Ida Chen; John M Connell; Ulf de Faire; Lisa de Las Fuentes; Renée de Mutsert; H Janaka de Silva; Jingzhong Ding; Anna F Dominiczak; Qing Duan; Charles B Eaton; Ruben N Eppinga; Jessica D Faul; Virginia Fisher; Terrence Forrester; Oscar H Franco; Yechiel Friedlander; Mohsen Ghanbari; Franco Giulianini; Hans J Grabe; Megan L Grove; C Charles Gu; Tamara B Harris; Sami Heikkinen; Chew-Kiat Heng; Makoto Hirata; James E Hixson; Barbara V Howard; M Arfan Ikram; David R Jacobs; Craig Johnson; Jost Bruno Jonas; Candace M Kammerer; Tomohiro Katsuya; Chiea Chuen Khor; Tuomas O Kilpeläinen; Woon-Puay Koh; Heikki A Koistinen; Ivana Kolcic; Charles Kooperberg; Jose E Krieger; Steve B Kritchevsky; Michiaki Kubo; Johanna Kuusisto; Timo A Lakka; Carl D Langefeld; Claudia Langenberg; Lenore J Launer; Benjamin Lehne; Rozenn N Lemaitre; Yize Li; Jingjing Liang; Jianjun Liu; Kiang Liu; Marie Loh; Tin Louie; Reedik Mägi; Ani W Manichaikul; Colin A McKenzie; Thomas Meitinger; Andres Metspalu; Yuri Milaneschi; Lili Milani; Karen L Mohlke; Thomas H Mosley; Kenneth J Mukamal; Mike A Nalls; Matthias Nauck; Christopher P Nelson; Nona Sotoodehnia; Jeff R O'Connell; Nicholette D Palmer; Raha Pazoki; Nancy L Pedersen; Annette Peters; Patricia A Peyser; Ozren Polasek; Neil Poulter; Leslie J Raffel; Olli T Raitakari; Alex P Reiner; Treva K Rice; Stephen S Rich; Antonietta Robino; Jennifer G Robinson; Lynda M Rose; Igor Rudan; Carsten O Schmidt; Pamela J Schreiner; William R Scott; Peter Sever; Yuan Shi; Stephen Sidney; Mario Sims; Blair H Smith; Jennifer A Smith; Harold Snieder; John M Starr; Konstantin Strauch; Nicholas Tan; Kent D Taylor; Yik Ying Teo; Yih Chung Tham; André G Uitterlinden; Diana van Heemst; Dragana Vuckovic; Melanie Waldenberger; Lihua Wang; Yujie Wang; Zhe Wang; Wen Bin Wei; Christine Williams; Gregory Wilson; Mary K Wojczynski; Jie Yao; Bing Yu; Caizheng Yu; Jian-Min Yuan; Wei Zhao; Alan B Zonderman; Diane M Becker; Michael Boehnke; Donald W Bowden; John C Chambers; Ian J Deary; Tõnu Esko; Martin Farrall; Paul W Franks; Barry I Freedman; Philippe Froguel; Paolo Gasparini; Christian Gieger; Bernardo L Horta; Yoichiro Kamatani; Norihiro Kato; Jaspal S Kooner; Markku Laakso; Karin Leander; Terho Lehtimäki; Patrik K E Magnusson; Brenda Penninx; Alexandre C Pereira; Rainer Rauramaa; Nilesh J Samani; James Scott; Xiao-Ou Shu; Pim van der Harst; Lynne E Wagenknecht; Ya Xing Wang; Nicholas J Wareham; Hugh Watkins; David R Weir; Ananda R Wickremasinghe; Wei Zheng; Paul Elliott; Kari E North; Claude Bouchard; Michele K Evans; Vilmundur Gudnason; Ching-Ti Liu; Yongmei Liu; Bruce M Psaty; Paul M Ridker; Rob M van Dam; Sharon L R Kardia; Xiaofeng Zhu; Charles N Rotimi; Dennis O Mook-Kanamori; Myriam Fornage; Tanika N Kelly; Ervin R Fox; Caroline Hayward; Cornelia M van Duijn; E Shyong Tai; Tien Yin Wong; Jingmin Liu; Jerome I Rotter; W James Gauderman; Michael A Province; Patricia B Munroe; Kenneth Rice; Daniel I Chasman; L Adrienne Cupples; Dabeeru C Rao; Alanna C Morrison Journal: Am J Epidemiol Date: 2019-06-01 Impact factor: 5.363
Authors: Dara O'Neill; Annie Britton; Mary K Hannah; Marcel Goldberg; Diana Kuh; Kay Tee Khaw; Steven Bell Journal: BMC Med Date: 2018-08-22 Impact factor: 8.775
Authors: Inge A T van de Luitgaarden; Sabine van Oort; Emma J Bouman; Linda J Schoonmade; Ilse C Schrieks; Diederick E Grobbee; Yvonne T van der Schouw; Susanna C Larsson; Stephen Burgess; Adriana J van Ballegooijen; N Charlotte Onland-Moret; Joline W J Beulens Journal: Eur J Epidemiol Date: 2021-08-22 Impact factor: 12.434