title: Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction.
abstract: 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.
authors: Department of Internal Medicine, CHA Gangnam Medical Center, School of Medicine, CHA University, Seoul 135-081, South Korea.
authors: Yunkyung
authors: Y
authors: Cho
authors: Institute for Clinical Research, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 463-712, South Korea.
authors: Jung O
authors: JO
authors: Kim
authors: Department of Emergency Medicine, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 463-712, South Korea.
authors: Jeong Han
authors: JH
authors: Lee
authors: Institute for Clinical Research, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 463-712, South Korea.
authors: Hye Mi
authors: HM
authors: Park
authors: Institute for Clinical Research, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 463-712, South Korea.
authors: Young Joo
authors: YJ
authors: Jeon
authors: Department of Neurology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 463-712, South Korea.
authors: Seung Hun
authors: SH
authors: Oh
authors: Department of Emergency Medicine, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 463-712, South Korea.
authors: Jinkun
authors: J
authors: Bae
authors: Department of Neurosurgery, Chungbuk National University Hospital, Chungbuk National University, Cheongju 361-711, South Korea.
authors: Young Seok
authors: YS
authors: Park
authors: Department of Neurology, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 463-712, South Korea.
authors: Ok Joon
authors: OJ
authors: Kim
authors: Institute for Clinical Research, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 463-712, South Korea.
authors: Nam Keun
authors: NK
authors: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D020520:Brain Infarction / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D058978:Reduced Folate Carrier Protein / Q000235:genetics* / Q000378:metabolism; D056910:Republic of Korea; D020521:Stroke / Q000097:blood / Q000235:genetics*; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D014805:Vitamin B 12