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

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.

• Authors: MyPhuong T Le, 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
• Journal: PloS one (PLoS One) Vol. 8 Issue 1 Pg. e52062 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23341889 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Glucose Transporter Type 2
• Glucose Transporter Type 5
• SLC2A2 protein, human
• SLC2A5 protein, human
• Uric Acid
• Fructokinases
• ketohexokinase

Topics

• Black or African American (genetics)
• Demography
• Female
• Fructokinases (genetics)
• Genetic Predisposition to Disease
• Glucose Transporter Type 2 (genetics)
• Glucose Transporter Type 5 (genetics)
• Humans
• Hypertension (blood, genetics, metabolism)
• Male
• Middle Aged
• Phenotype
• Polymorphism, Single Nucleotide (genetics)
• Uric Acid (blood)
• White People (genetics)