Gene-gene combination effect and interactions among ABCA1, APOA1, SR-B1, and CETP polymorphisms for serum high-density lipoprotein-cholesterol in the japanese population

Akihiko Nakamura, Hideshi Niimura, Kazuyo Kuwabara, Toshiro Takezaki, Emi Morita, Kenji Wakai, Nobuyuki Hamajima, Yuichiro Nishida, Tanvir Chowdhury Turin, Sadao Suzuki, Keizo Ohnaka, Hirokazu Uemura, Etsuko Ozaki, Satoyo Hosono, Haruo Mikami, Michiaki Kubo, Hideo Tanaka

Research output: Contribution to journalArticle

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Abstract

Abstract Background/Objective: Gene-gene interactions in the reverse cholesterol transport system for high-density lipoproteincholesterol (HDL-C) are poorly understood. The present study observed gene-gene combination effect and interactions between single nucleotide polymorphisms (SNPs) in ABCA1, APOA1, SR-B1, and CETP in serum HDL-C from a cross-sectional study in the Japanese population. Methods: The study population comprised 1,535 men and 1,515 women aged 35-69 years who were enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We selected 13 SNPs in the ABCA1, APOA1, CETP, and SR-B1 genes in the reverse cholesterol transport system. The effects of genetic and environmental factors were assessed using general linear and logistic regression models after adjusting for age, sex, and region. Principal Findings: Alcohol consumption and daily activity were positively associated with HDL-C levels, whereas smoking had a negative relationship. The T allele of CETP, rs3764261, was correlated with higher HDL-C levels and had the highest coefficient (2.93 mg/dL/allele) among the 13 SNPs, which was statistically significant after applying the Bonferroni correction (p<0.001). Gene-gene combination analysis revealed that CETP rs3764261 was associated with high HDL-C levels with any combination of SNPs from ABCA1 , APOA1, and SR-B1, although no gene-gene interaction was apparent. An increasing trend for serum HDL-C was also observed with an increasing number of alleles (p<0.001). Conclusions: The present study identified a multiplier effect from a polymorphism in CETP with ABCA1, APOA1, and SR-B1, as well as a dose-dependence according to the number of alleles present.

Original languageEnglish
Article numbere82046
JournalPloS one
Volume8
Issue number12
DOIs
Publication statusPublished - 20-12-2013

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Polymorphism
high density lipoprotein cholesterol
HDL Cholesterol
Genes
genetic polymorphism
single nucleotide polymorphism
Serum
Population
Single Nucleotide Polymorphism
genes
alleles
Nucleotides
gene interaction
Alleles
cholesterol
multipliers
Logistic Models
Cholesterol
cohort studies
cross-sectional studies

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Nakamura, Akihiko ; Niimura, Hideshi ; Kuwabara, Kazuyo ; Takezaki, Toshiro ; Morita, Emi ; Wakai, Kenji ; Hamajima, Nobuyuki ; Nishida, Yuichiro ; Turin, Tanvir Chowdhury ; Suzuki, Sadao ; Ohnaka, Keizo ; Uemura, Hirokazu ; Ozaki, Etsuko ; Hosono, Satoyo ; Mikami, Haruo ; Kubo, Michiaki ; Tanaka, Hideo. / Gene-gene combination effect and interactions among ABCA1, APOA1, SR-B1, and CETP polymorphisms for serum high-density lipoprotein-cholesterol in the japanese population. In: PloS one. 2013 ; Vol. 8, No. 12.
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title = "Gene-gene combination effect and interactions among ABCA1, APOA1, SR-B1, and CETP polymorphisms for serum high-density lipoprotein-cholesterol in the japanese population",
abstract = "Abstract Background/Objective: Gene-gene interactions in the reverse cholesterol transport system for high-density lipoproteincholesterol (HDL-C) are poorly understood. The present study observed gene-gene combination effect and interactions between single nucleotide polymorphisms (SNPs) in ABCA1, APOA1, SR-B1, and CETP in serum HDL-C from a cross-sectional study in the Japanese population. Methods: The study population comprised 1,535 men and 1,515 women aged 35-69 years who were enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We selected 13 SNPs in the ABCA1, APOA1, CETP, and SR-B1 genes in the reverse cholesterol transport system. The effects of genetic and environmental factors were assessed using general linear and logistic regression models after adjusting for age, sex, and region. Principal Findings: Alcohol consumption and daily activity were positively associated with HDL-C levels, whereas smoking had a negative relationship. The T allele of CETP, rs3764261, was correlated with higher HDL-C levels and had the highest coefficient (2.93 mg/dL/allele) among the 13 SNPs, which was statistically significant after applying the Bonferroni correction (p<0.001). Gene-gene combination analysis revealed that CETP rs3764261 was associated with high HDL-C levels with any combination of SNPs from ABCA1 , APOA1, and SR-B1, although no gene-gene interaction was apparent. An increasing trend for serum HDL-C was also observed with an increasing number of alleles (p<0.001). Conclusions: The present study identified a multiplier effect from a polymorphism in CETP with ABCA1, APOA1, and SR-B1, as well as a dose-dependence according to the number of alleles present.",
author = "Akihiko Nakamura and Hideshi Niimura and Kazuyo Kuwabara and Toshiro Takezaki and Emi Morita and Kenji Wakai and Nobuyuki Hamajima and Yuichiro Nishida and Turin, {Tanvir Chowdhury} and Sadao Suzuki and Keizo Ohnaka and Hirokazu Uemura and Etsuko Ozaki and Satoyo Hosono and Haruo Mikami and Michiaki Kubo and Hideo Tanaka",
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Nakamura, A, Niimura, H, Kuwabara, K, Takezaki, T, Morita, E, Wakai, K, Hamajima, N, Nishida, Y, Turin, TC, Suzuki, S, Ohnaka, K, Uemura, H, Ozaki, E, Hosono, S, Mikami, H, Kubo, M & Tanaka, H 2013, 'Gene-gene combination effect and interactions among ABCA1, APOA1, SR-B1, and CETP polymorphisms for serum high-density lipoprotein-cholesterol in the japanese population', PloS one, vol. 8, no. 12, e82046. https://doi.org/10.1371/journal.pone.0082046

Gene-gene combination effect and interactions among ABCA1, APOA1, SR-B1, and CETP polymorphisms for serum high-density lipoprotein-cholesterol in the japanese population. / Nakamura, Akihiko; Niimura, Hideshi; Kuwabara, Kazuyo; Takezaki, Toshiro; Morita, Emi; Wakai, Kenji; Hamajima, Nobuyuki; Nishida, Yuichiro; Turin, Tanvir Chowdhury; Suzuki, Sadao; Ohnaka, Keizo; Uemura, Hirokazu; Ozaki, Etsuko; Hosono, Satoyo; Mikami, Haruo; Kubo, Michiaki; Tanaka, Hideo.

In: PloS one, Vol. 8, No. 12, e82046, 20.12.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Gene-gene combination effect and interactions among ABCA1, APOA1, SR-B1, and CETP polymorphisms for serum high-density lipoprotein-cholesterol in the japanese population

AU - Nakamura, Akihiko

AU - Niimura, Hideshi

AU - Kuwabara, Kazuyo

AU - Takezaki, Toshiro

AU - Morita, Emi

AU - Wakai, Kenji

AU - Hamajima, Nobuyuki

AU - Nishida, Yuichiro

AU - Turin, Tanvir Chowdhury

AU - Suzuki, Sadao

AU - Ohnaka, Keizo

AU - Uemura, Hirokazu

AU - Ozaki, Etsuko

AU - Hosono, Satoyo

AU - Mikami, Haruo

AU - Kubo, Michiaki

AU - Tanaka, Hideo

PY - 2013/12/20

Y1 - 2013/12/20

N2 - Abstract Background/Objective: Gene-gene interactions in the reverse cholesterol transport system for high-density lipoproteincholesterol (HDL-C) are poorly understood. The present study observed gene-gene combination effect and interactions between single nucleotide polymorphisms (SNPs) in ABCA1, APOA1, SR-B1, and CETP in serum HDL-C from a cross-sectional study in the Japanese population. Methods: The study population comprised 1,535 men and 1,515 women aged 35-69 years who were enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We selected 13 SNPs in the ABCA1, APOA1, CETP, and SR-B1 genes in the reverse cholesterol transport system. The effects of genetic and environmental factors were assessed using general linear and logistic regression models after adjusting for age, sex, and region. Principal Findings: Alcohol consumption and daily activity were positively associated with HDL-C levels, whereas smoking had a negative relationship. The T allele of CETP, rs3764261, was correlated with higher HDL-C levels and had the highest coefficient (2.93 mg/dL/allele) among the 13 SNPs, which was statistically significant after applying the Bonferroni correction (p<0.001). Gene-gene combination analysis revealed that CETP rs3764261 was associated with high HDL-C levels with any combination of SNPs from ABCA1 , APOA1, and SR-B1, although no gene-gene interaction was apparent. An increasing trend for serum HDL-C was also observed with an increasing number of alleles (p<0.001). Conclusions: The present study identified a multiplier effect from a polymorphism in CETP with ABCA1, APOA1, and SR-B1, as well as a dose-dependence according to the number of alleles present.

AB - Abstract Background/Objective: Gene-gene interactions in the reverse cholesterol transport system for high-density lipoproteincholesterol (HDL-C) are poorly understood. The present study observed gene-gene combination effect and interactions between single nucleotide polymorphisms (SNPs) in ABCA1, APOA1, SR-B1, and CETP in serum HDL-C from a cross-sectional study in the Japanese population. Methods: The study population comprised 1,535 men and 1,515 women aged 35-69 years who were enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We selected 13 SNPs in the ABCA1, APOA1, CETP, and SR-B1 genes in the reverse cholesterol transport system. The effects of genetic and environmental factors were assessed using general linear and logistic regression models after adjusting for age, sex, and region. Principal Findings: Alcohol consumption and daily activity were positively associated with HDL-C levels, whereas smoking had a negative relationship. The T allele of CETP, rs3764261, was correlated with higher HDL-C levels and had the highest coefficient (2.93 mg/dL/allele) among the 13 SNPs, which was statistically significant after applying the Bonferroni correction (p<0.001). Gene-gene combination analysis revealed that CETP rs3764261 was associated with high HDL-C levels with any combination of SNPs from ABCA1 , APOA1, and SR-B1, although no gene-gene interaction was apparent. An increasing trend for serum HDL-C was also observed with an increasing number of alleles (p<0.001). Conclusions: The present study identified a multiplier effect from a polymorphism in CETP with ABCA1, APOA1, and SR-B1, as well as a dose-dependence according to the number of alleles present.

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U2 - 10.1371/journal.pone.0082046

DO - 10.1371/journal.pone.0082046

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

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