Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction

Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vas...

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Veröffentlicht in:PloS one 2015-02, Vol.10 (2), p.e0115295-e0115295
Hauptverfasser: Cho, Yunkyung, Kim, Jung O, Lee, Jeong Han, Park, Hye Mi, Jeon, Young Joo, Oh, Seung Hun, Bae, Jinkun, Park, Young Seok, Kim, Ok Joon, Kim, Nam Keun
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container_title PloS one
container_volume 10
creator Cho, Yunkyung
Kim, Jung O
Lee, Jeong Han
Park, Hye Mi
Jeon, Young Joo
Oh, Seung Hun
Bae, Jinkun
Park, Young Seok
Kim, Ok Joon
Kim, Nam Keun
description Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke.
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Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C&gt;T, 80A&gt;G, 696T&gt;C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2015 Cho et al 2015 Cho et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-e027d59ad43f7fd51f86189fcb547b7b204bee00f2a71a1cd594f8109f3f39403</citedby><cites>FETCH-LOGICAL-c593t-e027d59ad43f7fd51f86189fcb547b7b204bee00f2a71a1cd594f8109f3f39403</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/PMC4319782/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319782/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23853,27911,27912,53778,53780,79355,79356</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25659099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Sengupta, Shantanu</contributor><creatorcontrib>Cho, Yunkyung</creatorcontrib><creatorcontrib>Kim, Jung O</creatorcontrib><creatorcontrib>Lee, Jeong Han</creatorcontrib><creatorcontrib>Park, Hye Mi</creatorcontrib><creatorcontrib>Jeon, Young Joo</creatorcontrib><creatorcontrib>Oh, Seung Hun</creatorcontrib><creatorcontrib>Bae, Jinkun</creatorcontrib><creatorcontrib>Park, Young Seok</creatorcontrib><creatorcontrib>Kim, Ok Joon</creatorcontrib><creatorcontrib>Kim, Nam Keun</creatorcontrib><title>Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C&gt;T, 80A&gt;G, 696T&gt;C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. 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Kim, Jung O ; Lee, Jeong Han ; Park, Hye Mi ; Jeon, Young Joo ; Oh, Seung Hun ; Bae, Jinkun ; Park, Young Seok ; Kim, Ok Joon ; Kim, Nam Keun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-e027d59ad43f7fd51f86189fcb547b7b204bee00f2a71a1cd594f8109f3f39403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Anion exchanging</topic><topic>Asian Continental Ancestry Group</topic><topic>Brain</topic><topic>Brain infarction</topic><topic>Brain Infarction - blood</topic><topic>Brain Infarction - genetics</topic><topic>Brain research</topic><topic>Cerebral blood flow</topic><topic>Cerebral infarction</topic><topic>Diabetes</topic><topic>Disease</topic><topic>Ecological risk assessment</topic><topic>Electrocardiography</topic><topic>Emergency medical care</topic><topic>Environmental effects</topic><topic>Environmental factors</topic><topic>Female</topic><topic>Folic acid</topic><topic>Gene polymorphism</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genotypes</topic><topic>Health risk assessment</topic><topic>Health risks</topic><topic>Homocysteine</topic><topic>Humans</topic><topic>Infarction</topic><topic>Ischemia</topic><topic>Lung cancer</topic><topic>Male</topic><topic>Medicine</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Occlusion</topic><topic>Patients</topic><topic>Physiological aspects</topic><topic>Polymerase chain reaction</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Reduced Folate Carrier Protein - genetics</topic><topic>Reduced Folate Carrier Protein - metabolism</topic><topic>Regulators</topic><topic>Republic of Korea</topic><topic>Restriction fragment length polymorphism</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Stroke</topic><topic>Stroke - blood</topic><topic>Stroke - genetics</topic><topic>Studies</topic><topic>Substitution reactions</topic><topic>Vascular diseases</topic><topic>Veins &amp; 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Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C&gt;T, 80A&gt;G, 696T&gt;C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A&gt;G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C&gt;T, 80A&gt;G, and 696T&gt;C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C&gt;T, 80A&gt;G, and 696T&gt;C polymorphisms may be risk factors for ischemic stroke.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25659099</pmid><doi>10.1371/journal.pone.0115295</doi><oa>free_for_read</oa></addata></record>
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subjects Aged
Aged, 80 and over
Anion exchanging
Asian Continental Ancestry Group
Brain
Brain infarction
Brain Infarction - blood
Brain Infarction - genetics
Brain research
Cerebral blood flow
Cerebral infarction
Diabetes
Disease
Ecological risk assessment
Electrocardiography
Emergency medical care
Environmental effects
Environmental factors
Female
Folic acid
Gene polymorphism
Genes
Genetic aspects
Genotypes
Health risk assessment
Health risks
Homocysteine
Humans
Infarction
Ischemia
Lung cancer
Male
Medicine
Metabolism
Middle Aged
Neurology
NMR
Nuclear magnetic resonance
Occlusion
Patients
Physiological aspects
Polymerase chain reaction
Polymorphism
Polymorphism, Genetic
Reduced Folate Carrier Protein - genetics
Reduced Folate Carrier Protein - metabolism
Regulators
Republic of Korea
Restriction fragment length polymorphism
Risk analysis
Risk factors
Stroke
Stroke - blood
Stroke - genetics
Studies
Substitution reactions
Vascular diseases
Veins & arteries
Vitamin B
Vitamin B 12 - blood
Vitamin B12
title Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction
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