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Sci Rep. 2015 Nov 3;5:15888. doi: 10.1038/srep15888.

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

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Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Preventive Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Division of Cancer Registry, Prevention and Epidemiology, Chiba Cancer Center, Chiba, Japan.
Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan.
Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Public Health, Shiga University of Medical Science, Otsu, Japan.
Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama, Japan.


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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