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
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.
Sci Rep. 2015 Nov 3;5:15888. doi: 10.1038/srep15888.
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.
高尿酸血症是心血管风险无可争议且具有高度预测性的生物标志物。溶质载体家族17成员1（SLC17A1）在肝脏和肾脏中表达，含有可降低尿酸水平的强效单核苷酸多态性候选位点。因此，我们通过对日本普通人群进行大规模汇总分析的横断面研究，检测了可能抑制心血管危险因素且与肝功能有关的SLC17A1多态性（rs1165196、rs1179086和rs3757131）。利用日本多机构合作队列研究的数据，我们确定了1842名年龄在35至69岁之间、具备所需数据的男女参与者，并分析了他们的SLC17A1基因型。在男性中，逻辑回归分析显示，SLC17A1多态性（rs1165196和rs3757131）中的次要等位基因与低密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值>2.0相关（rs1165196：比值比[OR]，0.703；95%置信区间[CI]，0.536 - 0.922；rs3757131：OR，0.658；95% CI，0.500 - 0.866），且与同型半胱氨酸水平>10.0 nmol/mL相关（rs1165196：OR，0.544；95% CI，0.374 - 0.792；rs3757131：OR，0.509；95% CI，0.347 - 0.746）。因此，这些多态性对男性的胆固醇稳态和高同型半胱氨酸血症具有显性负性作用，与饮酒、身体活动或每日能量及营养摄入无关。因此，SLC17A1的基因变异是日本男性胆固醇稳态改变和高同型半胱氨酸血症的潜在生物标志物。
