Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men

Teruhide Koyama, Daisuke Matsui, Nagato Kuriyama, Etsuko Ozaki, Keitaro Tanaka, Isao Oze, Nobuyuki Hamajima, Kenji Wakai, Rieko Okada, Kokichi Arisawa, Haruo Mikami, Keiichi Shimatani, Akie Hirata, Naoyuki Takashima, Sadao Suzuki, Chisato Nagata, Michiaki Kubo, Hideo Tanaka

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Abstract

Hyperuricaemia is an undisputed and highly predictive biomarker for cardiovascular risk. SLC17A1, expressed in the liver and kidneys, harbours potent candidate single nucleotide polymorphisms that decrease uric acid levels. Therefore, we examined SLC17A1 polymorphisms (rs1165196, rs1179086, and rs3757131), which might suppress cardiovascular risk factors and that are involved in liver functioning, via a large-scale pooled analysis of the Japanese general population in a cross-sectional study. Using data from the Japan Multi-Institutional Collaborative Cohort Study, we identified 1842 participants of both sexes, 35-69-years-old, having the requisite data, and analysed their SLC17A1 genotypes. In men, logistic regression analyses revealed that minor alleles in SLC17A1 polymorphisms (rs1165196 and rs3757131) were associated with a low-/high-density lipoprotein cholesterol ratio >2.0 (rs1165196: odds ratio [OR], 0.703; 95% confidence interval [CI], 0.536-0.922; rs3757131: OR, 0.658; 95% CI, 0.500-0.866), and with homocysteine levels of >10.0 nmol/mL (rs1165196: OR, 0.544; 95% CI, 0.374-0.792; rs3757131: OR, 0.509; 95% CI, 0.347-0.746). Therefore, these polymorphisms had dominant negative effects on cholesterol homeostasis and hyperhomocysteinaemia, in men, independent of alcohol consumption, physical activity, or daily energy and nutrition intake. Thus, genetic variants of SLC17A1 are potential biomarkers for altered cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.

Original languageEnglish
Article number15888
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 03-11-2015

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Hyperhomocysteinemia
Homeostasis
Odds Ratio
Cholesterol
Confidence Intervals
Biomarkers
Liver
Homocysteine
Energy Intake
Uric Acid
Alcohol Drinking
LDL Cholesterol
HDL Cholesterol
Single Nucleotide Polymorphism
Japan
Cohort Studies
Cross-Sectional Studies
Logistic Models
Alleles
Genotype

All Science Journal Classification (ASJC) codes

  • General

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Koyama, Teruhide ; Matsui, Daisuke ; Kuriyama, Nagato ; Ozaki, Etsuko ; Tanaka, Keitaro ; Oze, Isao ; Hamajima, Nobuyuki ; Wakai, Kenji ; Okada, Rieko ; Arisawa, Kokichi ; Mikami, Haruo ; Shimatani, Keiichi ; Hirata, Akie ; Takashima, Naoyuki ; Suzuki, Sadao ; Nagata, Chisato ; Kubo, Michiaki ; Tanaka, Hideo. / Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men. In: Scientific reports. 2015 ; Vol. 5.
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title = "Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men",
abstract = "Hyperuricaemia is an undisputed and highly predictive biomarker for cardiovascular risk. SLC17A1, expressed in the liver and kidneys, harbours potent candidate single nucleotide polymorphisms that decrease uric acid levels. Therefore, we examined SLC17A1 polymorphisms (rs1165196, rs1179086, and rs3757131), which might suppress cardiovascular risk factors and that are involved in liver functioning, via a large-scale pooled analysis of the Japanese general population in a cross-sectional study. Using data from the Japan Multi-Institutional Collaborative Cohort Study, we identified 1842 participants of both sexes, 35-69-years-old, having the requisite data, and analysed their SLC17A1 genotypes. In men, logistic regression analyses revealed that minor alleles in SLC17A1 polymorphisms (rs1165196 and rs3757131) were associated with a low-/high-density lipoprotein cholesterol ratio >2.0 (rs1165196: odds ratio [OR], 0.703; 95{\%} confidence interval [CI], 0.536-0.922; rs3757131: OR, 0.658; 95{\%} CI, 0.500-0.866), and with homocysteine levels of >10.0 nmol/mL (rs1165196: OR, 0.544; 95{\%} CI, 0.374-0.792; rs3757131: OR, 0.509; 95{\%} CI, 0.347-0.746). Therefore, these polymorphisms had dominant negative effects on cholesterol homeostasis and hyperhomocysteinaemia, in men, independent of alcohol consumption, physical activity, or daily energy and nutrition intake. Thus, genetic variants of SLC17A1 are potential biomarkers for altered cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.",
author = "Teruhide Koyama and Daisuke Matsui and Nagato Kuriyama and Etsuko Ozaki and Keitaro Tanaka and Isao Oze and Nobuyuki Hamajima and Kenji Wakai and Rieko Okada and Kokichi Arisawa and Haruo Mikami and Keiichi Shimatani and Akie Hirata and Naoyuki Takashima and Sadao Suzuki and Chisato Nagata and Michiaki Kubo and Hideo Tanaka",
year = "2015",
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Koyama, T, Matsui, D, Kuriyama, N, Ozaki, E, Tanaka, K, Oze, I, Hamajima, N, Wakai, K, Okada, R, Arisawa, K, Mikami, H, Shimatani, K, Hirata, A, Takashima, N, Suzuki, S, Nagata, C, Kubo, M & Tanaka, H 2015, 'Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men', Scientific reports, vol. 5, 15888. https://doi.org/10.1038/srep15888

Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men. / Koyama, Teruhide; Matsui, Daisuke; Kuriyama, Nagato; Ozaki, Etsuko; Tanaka, Keitaro; Oze, Isao; Hamajima, Nobuyuki; Wakai, Kenji; Okada, Rieko; Arisawa, Kokichi; Mikami, Haruo; Shimatani, Keiichi; Hirata, Akie; Takashima, Naoyuki; Suzuki, Sadao; Nagata, Chisato; Kubo, Michiaki; Tanaka, Hideo.

In: Scientific reports, Vol. 5, 15888, 03.11.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic variants of SLC17A1 are associated with cholesterol homeostasis and hyperhomocysteinaemia in Japanese men

AU - Koyama, Teruhide

AU - Matsui, Daisuke

AU - Kuriyama, Nagato

AU - Ozaki, Etsuko

AU - Tanaka, Keitaro

AU - Oze, Isao

AU - Hamajima, Nobuyuki

AU - Wakai, Kenji

AU - Okada, Rieko

AU - Arisawa, Kokichi

AU - Mikami, Haruo

AU - Shimatani, Keiichi

AU - Hirata, Akie

AU - Takashima, Naoyuki

AU - Suzuki, Sadao

AU - Nagata, Chisato

AU - Kubo, Michiaki

AU - Tanaka, Hideo

PY - 2015/11/3

Y1 - 2015/11/3

N2 - Hyperuricaemia is an undisputed and highly predictive biomarker for cardiovascular risk. SLC17A1, expressed in the liver and kidneys, harbours potent candidate single nucleotide polymorphisms that decrease uric acid levels. Therefore, we examined SLC17A1 polymorphisms (rs1165196, rs1179086, and rs3757131), which might suppress cardiovascular risk factors and that are involved in liver functioning, via a large-scale pooled analysis of the Japanese general population in a cross-sectional study. Using data from the Japan Multi-Institutional Collaborative Cohort Study, we identified 1842 participants of both sexes, 35-69-years-old, having the requisite data, and analysed their SLC17A1 genotypes. In men, logistic regression analyses revealed that minor alleles in SLC17A1 polymorphisms (rs1165196 and rs3757131) were associated with a low-/high-density lipoprotein cholesterol ratio >2.0 (rs1165196: odds ratio [OR], 0.703; 95% confidence interval [CI], 0.536-0.922; rs3757131: OR, 0.658; 95% CI, 0.500-0.866), and with homocysteine levels of >10.0 nmol/mL (rs1165196: OR, 0.544; 95% CI, 0.374-0.792; rs3757131: OR, 0.509; 95% CI, 0.347-0.746). Therefore, these polymorphisms had dominant negative effects on cholesterol homeostasis and hyperhomocysteinaemia, in men, independent of alcohol consumption, physical activity, or daily energy and nutrition intake. Thus, genetic variants of SLC17A1 are potential biomarkers for altered cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.

AB - Hyperuricaemia is an undisputed and highly predictive biomarker for cardiovascular risk. SLC17A1, expressed in the liver and kidneys, harbours potent candidate single nucleotide polymorphisms that decrease uric acid levels. Therefore, we examined SLC17A1 polymorphisms (rs1165196, rs1179086, and rs3757131), which might suppress cardiovascular risk factors and that are involved in liver functioning, via a large-scale pooled analysis of the Japanese general population in a cross-sectional study. Using data from the Japan Multi-Institutional Collaborative Cohort Study, we identified 1842 participants of both sexes, 35-69-years-old, having the requisite data, and analysed their SLC17A1 genotypes. In men, logistic regression analyses revealed that minor alleles in SLC17A1 polymorphisms (rs1165196 and rs3757131) were associated with a low-/high-density lipoprotein cholesterol ratio >2.0 (rs1165196: odds ratio [OR], 0.703; 95% confidence interval [CI], 0.536-0.922; rs3757131: OR, 0.658; 95% CI, 0.500-0.866), and with homocysteine levels of >10.0 nmol/mL (rs1165196: OR, 0.544; 95% CI, 0.374-0.792; rs3757131: OR, 0.509; 95% CI, 0.347-0.746). Therefore, these polymorphisms had dominant negative effects on cholesterol homeostasis and hyperhomocysteinaemia, in men, independent of alcohol consumption, physical activity, or daily energy and nutrition intake. Thus, genetic variants of SLC17A1 are potential biomarkers for altered cholesterol homeostasis and hyperhomocysteinaemia in Japanese men.

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