Yasuharu Tabara1, Hidenori Arai2, Yuhko Hirao3, Yoshimitsu Takahashi4, Kazuya Setoh5, Takahisa Kawaguchi5, Shinji Kosugi6, Yasuki Ito3, Takeo Nakayama4, Fumihiko Matsuda5. 1. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: tabara@genome.med.kyoto-u.ac.jp. 2. National Center for Geriatrics and Gerontology, Obu, Japan. 3. Research and Development Center, Denka Seiken Co., Ltd., Tokyo, Japan. 4. Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan. 5. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. 6. Department of Medical Ethics and Medical Genetics, Kyoto University School of Public Health, Kyoto, Japan.
Abstract
BACKGROUND: Light-to-moderate alcohol consumption may increase circulating high-density lipoprotein cholesterol (HDL-C) levels and decrease low-density lipoprotein cholesterol (LDL-C) levels. However, the effect of alcohol on biologically important lipoprotein subfractions remains largely unknown. Here we aimed to clarify the effects of alcohol on lipoprotein subfractions using a Mendelian randomization analysis. METHODS: The study subjects consisted of 8364 general Japanese individuals. The rs671 polymorphism in aldehyde dehydrogenase 2 gene, a rate-controlling enzyme of alcohol metabolism, was used as an instrumental variable. Lipoprotein subfractions were measured by a homogeneous assay. RESULTS: The biologically active *1 allele of the ALDH2 genotype was strongly associated with alcohol consumption in men (p < 0.001). In a regression analysis adjusted for possible covariates, the *1 allele was positively associated with HDL-C even in a sub-analysis for HDL subfractions (HDL2-C: β = 0.082, p < 0.001; HDL3-C: β = 0.195, p < 0.001). In contrast, the *1 allele was inversely associated with total LDL-C levels (β = -0.049, p = 0.008), while its association with large-buoyant LDL-C (β = -0.124, p < 0.001) and small-dense LDL-C (β = 0.069, p < 0.001) was opposite. Therefore, the ratio of small-dense LDL to large-buoyant LDL exhibited a linear increase with the number of *1 alleles carried (β = 0.127, p < 0.001). Furthermore, the *1 allele was inversely associated with triglyceride levels in an analysis adjusted for LDL subfractions (β = -0.097, p < 0.001), but not for the total LDL (β = 0.014, p = 0.410). CONCLUSIONS: Alcohol may increase HDL-C levels irrespective of the particle size. Moreover, alcohol may decrease the total LDL-C, although the proportion of atherogenic small-dense LDL-C increased partially due to a potential inter-relationship with decreased triglyceride levels.
BACKGROUND: Light-to-moderate alcohol consumption may increase circulating high-density lipoprotein cholesterol (HDL-C) levels and decrease low-density lipoprotein cholesterol (LDL-C) levels. However, the effect of alcohol on biologically important lipoprotein subfractions remains largely unknown. Here we aimed to clarify the effects of alcohol on lipoprotein subfractions using a Mendelian randomization analysis. METHODS: The study subjects consisted of 8364 general Japanese individuals. The rs671 polymorphism in aldehyde dehydrogenase 2 gene, a rate-controlling enzyme of alcohol metabolism, was used as an instrumental variable. Lipoprotein subfractions were measured by a homogeneous assay. RESULTS: The biologically active *1 allele of the ALDH2 genotype was strongly associated with alcohol consumption in men (p < 0.001). In a regression analysis adjusted for possible covariates, the *1 allele was positively associated with HDL-C even in a sub-analysis for HDL subfractions (HDL2-C: β = 0.082, p < 0.001; HDL3-C: β = 0.195, p < 0.001). In contrast, the *1 allele was inversely associated with total LDL-C levels (β = -0.049, p = 0.008), while its association with large-buoyant LDL-C (β = -0.124, p < 0.001) and small-dense LDL-C (β = 0.069, p < 0.001) was opposite. Therefore, the ratio of small-dense LDL to large-buoyant LDL exhibited a linear increase with the number of *1 alleles carried (β = 0.127, p < 0.001). Furthermore, the *1 allele was inversely associated with triglyceride levels in an analysis adjusted for LDL subfractions (β = -0.097, p < 0.001), but not for the total LDL (β = 0.014, p = 0.410). CONCLUSIONS:Alcohol may increase HDL-C levels irrespective of the particle size. Moreover, alcohol may decrease the total LDL-C, although the proportion of atherogenic small-dense LDL-C increased partially due to a potential inter-relationship with decreased triglyceride levels.
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
Authors: Christopher R Stephens; Jonathan F Easton; Adriana Robles-Cabrera; Ruben Fossion; Lizbeth de la Cruz; Ricardo Martínez-Tapia; Antonio Barajas-Martínez; Alejandro Hernández-Chávez; Juan Antonio López-Rivera; Ana Leonor Rivera Journal: Front Public Health Date: 2020-05-20