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
N1 - Funding Information:
The authors thank Kyota Ashikawa, Tomomi Aoi, and the other members of the Laboratory for Genotyping Development, RIKEN Center for Genomic Medicine, for their support with the genotyping, as well as Yoko Mitsuda, Keiko Shibata, and Etsuko Kimura of the Department of Preventive Medicine, Nagoya University Graduate School of Medicine for their technical assistance. The authors also thank Shinkan Tokudome of the National Institute of Health and Nutrition (formerly Nagoya City University), Chiho Goto of Nagoya Bunri University, Nahomi Imaeda of Nagoya Women’s University, Yuko Tokudome of Nagoya University of Arts and Sciences, Masato Ikeda of the University of Occupational and Environmental Health, and Shinzo Maki of the Aichi Prefectural Dietetic Association for providing the food frequency questionnaire and a program to calculate the participants’ nutritional intake. This study was supported by Grants-in-Aid for Scientific Research on Priority Areas (No. 17015018) and Innovative Areas (No. 221S0001) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. The funding sources played no role in the study design; the collection, analysis and interpretation of data; the writing of this report; or the decision to submit this manuscript for publication.
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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U2 - 10.1038/srep15888
DO - 10.1038/srep15888
M3 - Article
C2 - 26524967
AN - SCOPUS:84946600223
SN - 2045-2322
VL - 5
JO - Scientific reports
JF - Scientific reports
M1 - 15888
ER -