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. 2013;8(1):e52062.
doi: 10.1371/journal.pone.0052062. Epub 2013 Jan 14.

Impact of genetic polymorphisms of SLC2A2, SLC2A5, and KHK on metabolic phenotypes in hypertensive individuals

MyPhuong T Le  1 , Maximilian T Lobmeyer, Marcus Campbell, Jing Cheng, Zhiying Wang, Stephen T Turner, Arlene B Chapman, Eric Boerwinkle, John G Gums, Yan Gong, Richard J Johnson, Julie A Johnson
Affiliations

Impact of genetic polymorphisms of SLC2A2, SLC2A5, and KHK on metabolic phenotypes in hypertensive individuals

MyPhuong T Le et al. PLoS One. 2013.

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.

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Conflict of interest statement

Competing Interests: RJJ has a patent application on inhibition of fructokinase as a mechanism to treat sugar craving and metabolic syndrome. The following lists the patent applications of RJJ: 1) U.S. Provisional application. TARGETING KHK FOR AMELIORATING OBESITY AND SUGAR CRAVING AND IMPROVING KIDNEY FUNCTION. Inventors Richard Johnson, Miguel Lanaspa, and Takuji Ishimoto. Serial No. US2011/046938. 2) U.S. Provisional Application. METHODS FOR FRUCTANASE AND FRUCTOKINASE INHIBITION. Inventors: Richard Johnson, Stephen Dreskin & Miguel Lanaspa-Garcia. Serial No. 61/563,806; Docket No. 11906-003; Ref: CU2981H-PPA1. RJJ also has two lay books, The Sugar Fix: The High-Fructose fallout That Is Making You Fat and Sick (Rodale and Simon and Schuster, 2008), and The Fat Switch (Mercola.com, 2012). None of the other authors declared a conflict of interest. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Effects of rs5438 and rs17033196 on SUA levels.
A. Effects of rs5438 on SUA levels in European Americans (EA) of PEAR. B. Effects of rs17033196 (tagged rs5438 r2 = 1) on SUA levels in European Americans of GERA I. ANOVA was adjusted for age and BMI and shown as least square mean ± standard error.
Figure 2
Figure 2. Effects of rs8192675 on HDL levels in PEAR and GERA European Americans.
ANOVA was adjusted for age, BMI, and sex and shown as least square mean ± standard error.
See this image and copyright information in PMC

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