Modification of the associations of alcohol intake with serum low-density lipoprotein cholesterol and triglyceriwdes by ALDH2 and ADH1B polymorphisms in Japanese men

Tae Sasakabe, Kenji Wakai, Sayo Kawai, Asahi Hishida, Mariko Naito, Sadao Suzuki, Yora Nindita, Kokichi Arisawa, Yoshikuni Kita, Megumi Hara, Nagato Kuriyama, Akie Hirata, Haruo Mikami, Isao Oze, Michiaki Kubo, Hideo Tanaka, Nobuyuki Hamajima

Research output: Contribution to journalArticle

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Abstract

Background: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. Methods: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. Results: The ALDH2 Glu=Lys or Lys=Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g=day was −2.49 mg=dL (95% confidence interval [CI], −3.85 to −1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His=His + ALDH2 Glu=Lys or Lys=Lys groups (−3.24 mg=dL, 95% CI, −5.03 to −1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His=His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu=Lys or Lys=Lys groups was replicated. Conclusions: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.

Original languageEnglish
Pages (from-to)185-193
Number of pages9
JournalJournal of epidemiology
Volume28
Issue number4
DOIs
Publication statusPublished - 01-01-2018

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LDL Cholesterol
Alcohols
Serum
Alcohol Drinking
Japan
Cohort Studies
Confidence Intervals
Lipids
Social Adjustment
Triglycerides
Alleles
Genotype
Regression Analysis
Enzymes

All Science Journal Classification (ASJC) codes

  • Epidemiology

Cite this

Sasakabe, Tae ; Wakai, Kenji ; Kawai, Sayo ; Hishida, Asahi ; Naito, Mariko ; Suzuki, Sadao ; Nindita, Yora ; Arisawa, Kokichi ; Kita, Yoshikuni ; Hara, Megumi ; Kuriyama, Nagato ; Hirata, Akie ; Mikami, Haruo ; Oze, Isao ; Kubo, Michiaki ; Tanaka, Hideo ; Hamajima, Nobuyuki. / Modification of the associations of alcohol intake with serum low-density lipoprotein cholesterol and triglyceriwdes by ALDH2 and ADH1B polymorphisms in Japanese men. In: Journal of epidemiology. 2018 ; Vol. 28, No. 4. pp. 185-193.
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title = "Modification of the associations of alcohol intake with serum low-density lipoprotein cholesterol and triglyceriwdes by ALDH2 and ADH1B polymorphisms in Japanese men",
abstract = "Background: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. Methods: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. Results: The ALDH2 Glu=Lys or Lys=Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g=day was −2.49 mg=dL (95{\%} confidence interval [CI], −3.85 to −1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His=His + ALDH2 Glu=Lys or Lys=Lys groups (−3.24 mg=dL, 95{\%} CI, −5.03 to −1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His=His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu=Lys or Lys=Lys groups was replicated. Conclusions: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.",
author = "Tae Sasakabe and Kenji Wakai and Sayo Kawai and Asahi Hishida and Mariko Naito and Sadao Suzuki and Yora Nindita and Kokichi Arisawa and Yoshikuni Kita and Megumi Hara and Nagato Kuriyama and Akie Hirata and Haruo Mikami and Isao Oze and Michiaki Kubo and Hideo Tanaka and Nobuyuki Hamajima",
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Sasakabe, T, Wakai, K, Kawai, S, Hishida, A, Naito, M, Suzuki, S, Nindita, Y, Arisawa, K, Kita, Y, Hara, M, Kuriyama, N, Hirata, A, Mikami, H, Oze, I, Kubo, M, Tanaka, H & Hamajima, N 2018, 'Modification of the associations of alcohol intake with serum low-density lipoprotein cholesterol and triglyceriwdes by ALDH2 and ADH1B polymorphisms in Japanese men', Journal of epidemiology, vol. 28, no. 4, pp. 185-193. https://doi.org/10.2188/jea.JE20160189

Modification of the associations of alcohol intake with serum low-density lipoprotein cholesterol and triglyceriwdes by ALDH2 and ADH1B polymorphisms in Japanese men. / Sasakabe, Tae; Wakai, Kenji; Kawai, Sayo; Hishida, Asahi; Naito, Mariko; Suzuki, Sadao; Nindita, Yora; Arisawa, Kokichi; Kita, Yoshikuni; Hara, Megumi; Kuriyama, Nagato; Hirata, Akie; Mikami, Haruo; Oze, Isao; Kubo, Michiaki; Tanaka, Hideo; Hamajima, Nobuyuki.

In: Journal of epidemiology, Vol. 28, No. 4, 01.01.2018, p. 185-193.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Modification of the associations of alcohol intake with serum low-density lipoprotein cholesterol and triglyceriwdes by ALDH2 and ADH1B polymorphisms in Japanese men

AU - Sasakabe, Tae

AU - Wakai, Kenji

AU - Kawai, Sayo

AU - Hishida, Asahi

AU - Naito, Mariko

AU - Suzuki, Sadao

AU - Nindita, Yora

AU - Arisawa, Kokichi

AU - Kita, Yoshikuni

AU - Hara, Megumi

AU - Kuriyama, Nagato

AU - Hirata, Akie

AU - Mikami, Haruo

AU - Oze, Isao

AU - Kubo, Michiaki

AU - Tanaka, Hideo

AU - Hamajima, Nobuyuki

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. Methods: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. Results: The ALDH2 Glu=Lys or Lys=Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g=day was −2.49 mg=dL (95% confidence interval [CI], −3.85 to −1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His=His + ALDH2 Glu=Lys or Lys=Lys groups (−3.24 mg=dL, 95% CI, −5.03 to −1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His=His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu=Lys or Lys=Lys groups was replicated. Conclusions: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.

AB - Background: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. Methods: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. Results: The ALDH2 Glu=Lys or Lys=Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g=day was −2.49 mg=dL (95% confidence interval [CI], −3.85 to −1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His=His + ALDH2 Glu=Lys or Lys=Lys groups (−3.24 mg=dL, 95% CI, −5.03 to −1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His=His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu=Lys or Lys=Lys groups was replicated. Conclusions: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.

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U2 - 10.2188/jea.JE20160189

DO - 10.2188/jea.JE20160189

M3 - Article

C2 - 29176272

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