Associations between dietary vitamin intake, ABCA1 gene promoter DNA methylation, and lipid profiles in a Japanese population

Ryosuke Fujii, Hiroya Yamada, Eiji Munetsuna, Mirai Yamazaki, Yoshitaka Ando, Genki Mizuno, Yoshiki Tsuboi, Koji Ohashi, Hiroaki Ishikawa, Chiharu Hagiwara, Keisuke Maeda, Shuji Hashimoto, Koji Suzuki

Research output: Contribution to journalArticle

Abstract

Background: Higher intake of fruits and vegetables is associated with reduced risk of specific types of cancer and of cardiovascular disease (CVD), but the protective role of the vitamins contained in fruits and vegetables on CVD is controversial. This discrepancy can raise the question of the effects of antioxidants in vitamins on CVD. Recently, we reported that higher vegetable intake was significantly associated with the decreased DNA methylation level of ATP-binding cassette transporter A1 (ABCA1), a gene associated with HDL-cholesterol metabolism. Objective: We investigated whether ABCA1 DNA methylation mediates an effect of dietary vitamin intake on lipid profiles, an important risk factor for CVD, in a Japanese population. Methods: A total of 225 individuals (108 men and 117 women) with no clinical history and no drug use for dyslipidemia participated in this cross-sectional study. We used the pyrosequencing method to measure the ABCA1 DNA methylation levels at 8 CpG sites, and we used mean DNA methylation level in statistical analysis. Dietary vitamin intake was assessed with the FFQ and adjusted for the residual method. Results: In women, higher dietary vitamin intake [vitamin A, β-carotene, folic acid, vitamin C (VC), vitamin D, and vitamin E] was significantly associated with lower mean ABCA1 DNA methylation levels (P = 0.004, 0.03, 0.005, 0.001, 0.03, and 0.04, respectively). In addition, in women, we found a significant inverse association between mean ABCA1 DNA methylation and HDL cholesterol (P = 0.04) but not for other lipid indexes. Mediation analysis showed a significant indirect effect of VC intake on HDL cholesterol through ABCA1 DNA methylation level in women (P = 0.04). Conclusions: Although this study does not prove causality, the results suggest that ABCA1 DNA methylation mediates the protective effect of VC on HDL cholesterol in women, which could offer a novel biological mechanism in CVD prevention.

Original languageEnglish
Pages (from-to)1213-1219
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Volume110
Issue number5
DOIs
Publication statusPublished - 01-11-2019

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ATP-Binding Cassette Transporters
DNA Methylation
Vitamins
Lipids
Cardiovascular Diseases
HDL Cholesterol
Population
Genes
Vegetables
Ascorbic Acid
Fruit
Carotenoids
Dyslipidemias
Vitamin A
Vitamin E
Folic Acid
Vitamin D
Causality
Cross-Sectional Studies
Antioxidants

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

@article{53b7e69572894deca53c5192ee95fd1d,
title = "Associations between dietary vitamin intake, ABCA1 gene promoter DNA methylation, and lipid profiles in a Japanese population",
abstract = "Background: Higher intake of fruits and vegetables is associated with reduced risk of specific types of cancer and of cardiovascular disease (CVD), but the protective role of the vitamins contained in fruits and vegetables on CVD is controversial. This discrepancy can raise the question of the effects of antioxidants in vitamins on CVD. Recently, we reported that higher vegetable intake was significantly associated with the decreased DNA methylation level of ATP-binding cassette transporter A1 (ABCA1), a gene associated with HDL-cholesterol metabolism. Objective: We investigated whether ABCA1 DNA methylation mediates an effect of dietary vitamin intake on lipid profiles, an important risk factor for CVD, in a Japanese population. Methods: A total of 225 individuals (108 men and 117 women) with no clinical history and no drug use for dyslipidemia participated in this cross-sectional study. We used the pyrosequencing method to measure the ABCA1 DNA methylation levels at 8 CpG sites, and we used mean DNA methylation level in statistical analysis. Dietary vitamin intake was assessed with the FFQ and adjusted for the residual method. Results: In women, higher dietary vitamin intake [vitamin A, β-carotene, folic acid, vitamin C (VC), vitamin D, and vitamin E] was significantly associated with lower mean ABCA1 DNA methylation levels (P = 0.004, 0.03, 0.005, 0.001, 0.03, and 0.04, respectively). In addition, in women, we found a significant inverse association between mean ABCA1 DNA methylation and HDL cholesterol (P = 0.04) but not for other lipid indexes. Mediation analysis showed a significant indirect effect of VC intake on HDL cholesterol through ABCA1 DNA methylation level in women (P = 0.04). Conclusions: Although this study does not prove causality, the results suggest that ABCA1 DNA methylation mediates the protective effect of VC on HDL cholesterol in women, which could offer a novel biological mechanism in CVD prevention.",
author = "Ryosuke Fujii and Hiroya Yamada and Eiji Munetsuna and Mirai Yamazaki and Yoshitaka Ando and Genki Mizuno and Yoshiki Tsuboi and Koji Ohashi and Hiroaki Ishikawa and Chiharu Hagiwara and Keisuke Maeda and Shuji Hashimoto and Koji Suzuki",
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Associations between dietary vitamin intake, ABCA1 gene promoter DNA methylation, and lipid profiles in a Japanese population. / Fujii, Ryosuke; Yamada, Hiroya; Munetsuna, Eiji; Yamazaki, Mirai; Ando, Yoshitaka; Mizuno, Genki; Tsuboi, Yoshiki; Ohashi, Koji; Ishikawa, Hiroaki; Hagiwara, Chiharu; Maeda, Keisuke; Hashimoto, Shuji; Suzuki, Koji.

In: American Journal of Clinical Nutrition, Vol. 110, No. 5, 01.11.2019, p. 1213-1219.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Associations between dietary vitamin intake, ABCA1 gene promoter DNA methylation, and lipid profiles in a Japanese population

AU - Fujii, Ryosuke

AU - Yamada, Hiroya

AU - Munetsuna, Eiji

AU - Yamazaki, Mirai

AU - Ando, Yoshitaka

AU - Mizuno, Genki

AU - Tsuboi, Yoshiki

AU - Ohashi, Koji

AU - Ishikawa, Hiroaki

AU - Hagiwara, Chiharu

AU - Maeda, Keisuke

AU - Hashimoto, Shuji

AU - Suzuki, Koji

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Background: Higher intake of fruits and vegetables is associated with reduced risk of specific types of cancer and of cardiovascular disease (CVD), but the protective role of the vitamins contained in fruits and vegetables on CVD is controversial. This discrepancy can raise the question of the effects of antioxidants in vitamins on CVD. Recently, we reported that higher vegetable intake was significantly associated with the decreased DNA methylation level of ATP-binding cassette transporter A1 (ABCA1), a gene associated with HDL-cholesterol metabolism. Objective: We investigated whether ABCA1 DNA methylation mediates an effect of dietary vitamin intake on lipid profiles, an important risk factor for CVD, in a Japanese population. Methods: A total of 225 individuals (108 men and 117 women) with no clinical history and no drug use for dyslipidemia participated in this cross-sectional study. We used the pyrosequencing method to measure the ABCA1 DNA methylation levels at 8 CpG sites, and we used mean DNA methylation level in statistical analysis. Dietary vitamin intake was assessed with the FFQ and adjusted for the residual method. Results: In women, higher dietary vitamin intake [vitamin A, β-carotene, folic acid, vitamin C (VC), vitamin D, and vitamin E] was significantly associated with lower mean ABCA1 DNA methylation levels (P = 0.004, 0.03, 0.005, 0.001, 0.03, and 0.04, respectively). In addition, in women, we found a significant inverse association between mean ABCA1 DNA methylation and HDL cholesterol (P = 0.04) but not for other lipid indexes. Mediation analysis showed a significant indirect effect of VC intake on HDL cholesterol through ABCA1 DNA methylation level in women (P = 0.04). Conclusions: Although this study does not prove causality, the results suggest that ABCA1 DNA methylation mediates the protective effect of VC on HDL cholesterol in women, which could offer a novel biological mechanism in CVD prevention.

AB - Background: Higher intake of fruits and vegetables is associated with reduced risk of specific types of cancer and of cardiovascular disease (CVD), but the protective role of the vitamins contained in fruits and vegetables on CVD is controversial. This discrepancy can raise the question of the effects of antioxidants in vitamins on CVD. Recently, we reported that higher vegetable intake was significantly associated with the decreased DNA methylation level of ATP-binding cassette transporter A1 (ABCA1), a gene associated with HDL-cholesterol metabolism. Objective: We investigated whether ABCA1 DNA methylation mediates an effect of dietary vitamin intake on lipid profiles, an important risk factor for CVD, in a Japanese population. Methods: A total of 225 individuals (108 men and 117 women) with no clinical history and no drug use for dyslipidemia participated in this cross-sectional study. We used the pyrosequencing method to measure the ABCA1 DNA methylation levels at 8 CpG sites, and we used mean DNA methylation level in statistical analysis. Dietary vitamin intake was assessed with the FFQ and adjusted for the residual method. Results: In women, higher dietary vitamin intake [vitamin A, β-carotene, folic acid, vitamin C (VC), vitamin D, and vitamin E] was significantly associated with lower mean ABCA1 DNA methylation levels (P = 0.004, 0.03, 0.005, 0.001, 0.03, and 0.04, respectively). In addition, in women, we found a significant inverse association between mean ABCA1 DNA methylation and HDL cholesterol (P = 0.04) but not for other lipid indexes. Mediation analysis showed a significant indirect effect of VC intake on HDL cholesterol through ABCA1 DNA methylation level in women (P = 0.04). Conclusions: Although this study does not prove causality, the results suggest that ABCA1 DNA methylation mediates the protective effect of VC on HDL cholesterol in women, which could offer a novel biological mechanism in CVD prevention.

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