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.
authors.affiliation: Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Teruhide
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsui
authors.affiliation: Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Nagato
authors.initials: N
authors.lastname: Kuriyama
authors.affiliation: Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Ozaki
authors.affiliation: Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Oze
authors.affiliation: Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.affiliation: Department of Preventive Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Kokichi
authors.initials: K
authors.lastname: Arisawa
authors.affiliation: Division of Cancer Registry, Prevention and Epidemiology, Chiba Cancer Center, Chiba, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Mikami
authors.affiliation: Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Shimatani
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Akie
authors.initials: A
authors.lastname: Hirata
authors.affiliation: Department of Public Health, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takashima
authors.affiliation: Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Nagata
authors.affiliation: Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D020138:Hyperhomocysteinemia / Q000208:ethnology / Q000235:genetics*; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D050609:Sodium-Phosphate Cotransporter Proteins, Type I / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C493546:SLC17A1 protein, human; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D002784:Cholesterol