Impact of Genetic Polymorphisms of SLC2A2, SLC2A5, and KHK on Metabolic Phenotypes in Hypertensive Individuals

• Type of Material: Article
• Authors: MyPhuong T Le, University of Florida; Maximilian T. Lobmeyer, University of Florida; Marcus Campbell, University of Florida; Jing Cheng, University of Florida; Zhiying Wang, University of Texas Health Science Center; Stephen T. Turner, Mayo Clinic; Arlene Chapman, Emory University; Eric Boerwinkle, University of Texas Health Science Center; John G. Gums, University of Florida; Yan Gong, University of Florida; Richard J. Johnson, University of Colorado Denver; Julie A. Johnson, University of Florida
• Language: English
• Date: 2013-01-14
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Le et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0052062
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 1
• Start Page: e52062
• End Page: e52062
• Grant/Funding Information: This work is supported by a grants from the National Institutes of Health (Bethesda, MD), grant #U01 GM074492, funded as part of the Pharmacogenetics Research Network (PEAR) and R01HL53330 (GERA I and II).; Additional support for this work includes: CTSA grants UL1-RR029890 (University of Florida), UL1-RR025008 (Emory University), and UL1-RR024150 (Mayo Clinic); and funds from the Mayo Foundation. M. Le was supported by institutional National Institutes of Health training grant (T32-DK007518-23) in the Division of Nephrology, University of Florida.; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: MULTIDISCIPLINARY SCIENCES; DENSITY-LIPOPROTEIN CHOLESTEROL; FANCONI-BICKEL-SYNDROME; FRUCTOSE-SWEETENED BEVERAGES; KIDNEY-DISEASE; ANTIHYPERTENSIVE RESPONSE; GENOMIC ASSOCIATION; SERUM URIC-ACID; Science & Technology; CARDIOVASCULAR-DISEASE; Multidisciplinary Sciences; SINGLE-NUCLEOTIDE POLYMORPHISMS; CORONARY-HEART-DISEASE; Science & Technology - Other Topics
• Research Categories: Biology, Molecular; Biology, Genetics; Health Sciences, Epidemiology

Abstract

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.