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


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.
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
MyPhuong T
MT
Le
Maximilian T
MT
Lobmeyer
Marcus
M
Campbell
Jing
J
Cheng
Zhiying
Z
Wang
Stephen T
ST
Turner
Arlene B
AB
Chapman
Eric
E
Boerwinkle
John G
JG
Gums
Yan
Y
Gong
Richard J
RJ
Johnson
Julie A
JA
Johnson
D001741:Black or African American / Q000235:genetics; D003710:Demography; D005260:Female; D005631:Fructokinases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D051273:Glucose Transporter Type 2 / Q000235:genetics*; D051296:Glucose Transporter Type 5 / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014527:Uric Acid / Q000097:blood; D044465:White People / Q000235:genetics
D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; C495680:SLC2A2 protein, human; C495726:SLC2A5 protein, human; D014527:Uric Acid; D005631:Fructokinases; C021475:ketohexokinase