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

All Science Journal Classification (ASJC) codes

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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, 5, [15888]. https://doi.org/10.1038/srep15888