SLC2A2、SLC2A5 和 KHK 基因多态性对高血压患者代谢表型的影响。
Impact of genetic polymorphisms of SLC2A2, SLC2A5, and KHK on metabolic phenotypes in hypertensive individuals.
机构信息
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
出版信息
PLoS One. 2013;8(1):e52062. doi: 10.1371/journal.pone.0052062. Epub 2013 Jan 14.
OBJECTIVE
In the past few decades, consumption of added sugars has increased dramatically. Studies have linked high sugar intake with increased risk for a number of diseases. Importantly, fructose, a component of sugar, has been linked with the development of features of metabolic syndrome. This study determined if single nucleotide polymorphisms in genes involved in fructose transport (solute carrier family 2 facilitated glucose transporter, member 2 (SLC2A2) and solute carrier family 2 facilitated glucose/fructose transporter, member 5 (SLC2A5)) and metabolism (ketohexokinase (KHK)) affect inter-individual variability in metabolic phenotypes, such as increased serum uric acid levels.
MATERIALS/METHODS: The influence of SLC2A2, SLC2A5, and KHK SNPs on metabolic phenotypes was tested in 237 European Americans and 167 African Americans from the Pharmacogenomic Evaluation and Antihypertensive Responses (PEAR) study. Using baseline untreated fasting data, associations were considered significant if p≤0.005. These SNPs were then evaluated for potential replication (p≤0.05) using data from the Genetic Epidemiology of Responses to Antihypertensives (GERA) studies.
RESULTS
SLC2A5 rs5438 was associated with an increase in serum uric acid in European American males. However, we were unable to replicate the association in GERA. The minor allele of SLC2A2 rs8192675 showed an association with lower high-density lipoproteins in European Americans (A/A: 51.0 mg/dL, A/G: 47.0 mg/dL, G/G: 41.5 mg/dL, p = 0.0034) in PEAR. The association between rs8192675 and lower high-density lipoproteins was replicated in the combined European American GERA study samples (A/A: 47.6 mg/dL, A/G: 48.6 mg/dL, G/G: 41.9 mg/dL, p = 0.0315).
CONCLUSIONS
The association between SLC2A2 rs8192675 and high-density lipoproteins suggests the polymorphism may play a role in influencing high-density lipoproteins and thus metabolic risk of cardiovascular disease.
目的
在过去的几十年中，添加糖的摄入量急剧增加。研究表明，高糖摄入与多种疾病的风险增加有关。重要的是，果糖是糖的一种成分，与代谢综合征特征的发展有关。本研究旨在确定参与果糖转运（溶质载体家族 2 易化葡萄糖转运蛋白，成员 2（SLC2A2）和溶质载体家族 2 易化葡萄糖/果糖转运蛋白，成员 5（SLC2A5））和代谢（己酮激酶（KHK））的基因中的单核苷酸多态性是否会影响个体间代谢表型的变异性，例如血清尿酸水平升高。
材料/方法：在 Pharmacogenomic Evaluation and Antihypertensive Responses (PEAR) 研究中，对 237 名欧洲裔美国人和 167 名非裔美国人的 SLC2A2、SLC2A5 和 KHK SNPs 对代谢表型的影响进行了测试。使用未经治疗的空腹基线数据，如果 p≤0.005，则认为关联具有统计学意义。然后，使用 Genetic Epidemiology of Responses to Antihypertensives (GERA) 研究的数据评估这些 SNP 复制的可能性（p≤0.05）。
结果
SLC2A5 rs5438 与欧洲裔美国男性血清尿酸升高有关。然而，我们无法在 GERA 中复制该关联。SLC2A2 rs8192675 的次要等位基因与欧洲裔美国人的高密度脂蛋白降低有关（A/A：51.0 mg/dL，A/G：47.0 mg/dL，G/G：41.5 mg/dL，p = 0.0034）在 PEAR 中。rs8192675 与高密度脂蛋白降低之间的关联在欧洲裔美国人 GERA 研究样本的合并样本中得到了复制（A/A：47.6 mg/dL，A/G：48.6 mg/dL，G/G：41.9 mg/dL，p = 0.0315）。
结论
SLC2A2 rs8192675 与高密度脂蛋白之间的关联表明，该多态性可能在影响高密度脂蛋白和心血管疾病代谢风险方面发挥作用。
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