Impact of genetic polymorphisms of SLC2A2, SLC2A5, and KHK on metabolic phenotypes in hypertensive individuals
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 determi...
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description | 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.
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.
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).
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. |
doi_str_mv | 10.1371/journal.pone.0052062 |
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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.
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).
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0052062</identifier><identifier>PMID: 23341889</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; African Americans ; African Americans - genetics ; Antihypertensives ; Biology ; Blood lipids ; Blood pressure ; Cardiovascular disease ; Cardiovascular diseases ; Cholesterol ; Chromosomes ; Demography ; Density ; Development and progression ; Diabetes ; Drug therapy ; Epidemiology ; European Continental Ancestry Group - genetics ; Female ; Fructokinases - genetics ; Fructose ; Genes ; Genetic aspects ; Genetic Predisposition to Disease ; Genomes ; Glucose ; Glucose transporter ; Glucose Transporter Type 2 - genetics ; Glucose Transporter Type 5 - genetics ; Health risks ; Humans ; Hypertension ; Hypertension - blood ; Hypertension - genetics ; Hypertension - metabolism ; Insulin ; Ketohexokinase ; Kidney diseases ; Lipoproteins ; Low density lipoprotein ; Male ; Males ; Medical research ; Medicine ; Metabolic disorders ; Metabolic syndrome ; Metabolism ; Middle Aged ; Minority & ethnic groups ; Pharmacogenomics ; Pharmacology ; Pharmacy ; Phenotype ; Phenotypes ; Polymorphism ; Polymorphism, Single Nucleotide - genetics ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Studies ; Sugar ; Type 2 diabetes ; Uric acid ; Uric Acid - blood</subject><ispartof>PloS one, 2013-01, Vol.8 (1), p.e52062-e52062</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Le et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Le et al 2013 Le et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-39f29e95199f5d799b2e7dd2583fd2aa9a9b4ba92eca796803a767ff15b72f0f3</citedby><cites>FETCH-LOGICAL-c692t-39f29e95199f5d799b2e7dd2583fd2aa9a9b4ba92eca796803a767ff15b72f0f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544854/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544854/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23341889$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Marian, Ali J.</contributor><creatorcontrib>Le, MyPhuong T</creatorcontrib><creatorcontrib>Lobmeyer, Maximilian T</creatorcontrib><creatorcontrib>Campbell, Marcus</creatorcontrib><creatorcontrib>Cheng, Jing</creatorcontrib><creatorcontrib>Wang, Zhiying</creatorcontrib><creatorcontrib>Turner, Stephen T</creatorcontrib><creatorcontrib>Chapman, Arlene B</creatorcontrib><creatorcontrib>Boerwinkle, Eric</creatorcontrib><creatorcontrib>Gums, John G</creatorcontrib><creatorcontrib>Gong, Yan</creatorcontrib><creatorcontrib>Johnson, Richard J</creatorcontrib><creatorcontrib>Johnson, Julie A</creatorcontrib><title>Impact of genetic polymorphisms of SLC2A2, SLC2A5, and KHK on metabolic phenotypes in hypertensive individuals</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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).
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.</description><subject>Acids</subject><subject>African Americans</subject><subject>African Americans - genetics</subject><subject>Antihypertensives</subject><subject>Biology</subject><subject>Blood lipids</subject><subject>Blood pressure</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cholesterol</subject><subject>Chromosomes</subject><subject>Demography</subject><subject>Density</subject><subject>Development and progression</subject><subject>Diabetes</subject><subject>Drug therapy</subject><subject>Epidemiology</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Female</subject><subject>Fructokinases - genetics</subject><subject>Fructose</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Predisposition to Disease</subject><subject>Genomes</subject><subject>Glucose</subject><subject>Glucose transporter</subject><subject>Glucose Transporter Type 2 - genetics</subject><subject>Glucose Transporter Type 5 - genetics</subject><subject>Health risks</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - blood</subject><subject>Hypertension - genetics</subject><subject>Hypertension - metabolism</subject><subject>Insulin</subject><subject>Ketohexokinase</subject><subject>Kidney diseases</subject><subject>Lipoproteins</subject><subject>Low density lipoprotein</subject><subject>Male</subject><subject>Males</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Metabolic disorders</subject><subject>Metabolic syndrome</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Minority & ethnic groups</subject><subject>Pharmacogenomics</subject><subject>Pharmacology</subject><subject>Pharmacy</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><subject>Sugar</subject><subject>Type 2 diabetes</subject><subject>Uric acid</subject><subject>Uric Acid - 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genetics</topic><topic>Antihypertensives</topic><topic>Biology</topic><topic>Blood lipids</topic><topic>Blood pressure</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cholesterol</topic><topic>Chromosomes</topic><topic>Demography</topic><topic>Density</topic><topic>Development and progression</topic><topic>Diabetes</topic><topic>Drug therapy</topic><topic>Epidemiology</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Female</topic><topic>Fructokinases - genetics</topic><topic>Fructose</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Predisposition to Disease</topic><topic>Genomes</topic><topic>Glucose</topic><topic>Glucose transporter</topic><topic>Glucose Transporter Type 2 - genetics</topic><topic>Glucose Transporter Type 5 - genetics</topic><topic>Health risks</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension - blood</topic><topic>Hypertension - genetics</topic><topic>Hypertension - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Le, MyPhuong T</au><au>Lobmeyer, Maximilian T</au><au>Campbell, Marcus</au><au>Cheng, Jing</au><au>Wang, Zhiying</au><au>Turner, Stephen T</au><au>Chapman, Arlene B</au><au>Boerwinkle, Eric</au><au>Gums, John G</au><au>Gong, Yan</au><au>Johnson, Richard J</au><au>Johnson, Julie A</au><au>Marian, Ali J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of genetic polymorphisms of SLC2A2, SLC2A5, and KHK on metabolic phenotypes in hypertensive individuals</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-01-14</date><risdate>2013</risdate><volume>8</volume><issue>1</issue><spage>e52062</spage><epage>e52062</epage><pages>e52062-e52062</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.
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.
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).
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23341889</pmid><doi>10.1371/journal.pone.0052062</doi><tpages>e52062</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2013-01, Vol.8 (1), p.e52062-e52062 |
issn | 1932-6203 1932-6203 |
language | eng |
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source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Acids African Americans African Americans - genetics Antihypertensives Biology Blood lipids Blood pressure Cardiovascular disease Cardiovascular diseases Cholesterol Chromosomes Demography Density Development and progression Diabetes Drug therapy Epidemiology European Continental Ancestry Group - genetics Female Fructokinases - genetics Fructose Genes Genetic aspects Genetic Predisposition to Disease Genomes Glucose Glucose transporter Glucose Transporter Type 2 - genetics Glucose Transporter Type 5 - genetics Health risks Humans Hypertension Hypertension - blood Hypertension - genetics Hypertension - metabolism Insulin Ketohexokinase Kidney diseases Lipoproteins Low density lipoprotein Male Males Medical research Medicine Metabolic disorders Metabolic syndrome Metabolism Middle Aged Minority & ethnic groups Pharmacogenomics Pharmacology Pharmacy Phenotype Phenotypes Polymorphism Polymorphism, Single Nucleotide - genetics Single nucleotide polymorphisms Single-nucleotide polymorphism Studies Sugar Type 2 diabetes Uric acid Uric Acid - blood |
title | Impact of genetic polymorphisms of SLC2A2, SLC2A5, and KHK on metabolic phenotypes in hypertensive individuals |
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