Association of Reduced Folate Carrier-1 (RFC-1) Polymorphisms with Ischemic Stroke and Silent Brain Infarction

<div><p>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 <i>RFC-1</i> 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 <i>RFC-1</i> polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the <i>RFC-1</i> -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The <i>RFC-1</i> 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the <i>RFC-1</i> -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 <i>RFC-1</i> -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke.</p></div

Comparison of genotype frequencies and AOR for the <i>RFC-1</i> -43C>T, 80A>G, and 696T>C polymorphisms between the ischemic stroke subgroups with small-artery occlusion, large-artery occlusion, cardio embolism, undetermined and control subjects.

<p>Comparison of genotype frequencies and AOR for the <i>RFC-1</i> -43C>T, 80A>G, and 696T>C polymorphisms between the ischemic stroke subgroups with small-artery occlusion, large-artery occlusion, cardio embolism, undetermined and control subjects.</p

Combined effects of genotype and homocysteine and folate levels upon ischemic stroke and silent brain infarction (SBI) risk.

<p>Combined effects of genotype and homocysteine and folate levels upon ischemic stroke and silent brain infarction (SBI) risk.</p

The haplotype analysis of the <i>RFC-1</i> -43C>T, 80A>G, and 696T>C polymorphisms among the ischemic stroke patients, silent brain infarction (SBI) patients, and control subjects.

<p>The haplotype analysis of the <i>RFC-1</i> -43C>T, 80A>G, and 696T>C polymorphisms among the ischemic stroke patients, silent brain infarction (SBI) patients, and control subjects.</p

Baseline characteristics of ischemic stroke patients, silent brain infarction (SBI) patients, and control subjects.

<p>Baseline characteristics of ischemic stroke patients, silent brain infarction (SBI) patients, and control subjects.</p

Comparison of genotype frequencies and AOR values for the <i>RFC-1</i> -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke patients, silent brain infarction (SBI) patients, and control subjects.

<p>Comparison of genotype frequencies and AOR values for the <i>RFC-1</i> -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke patients, silent brain infarction (SBI) patients, and control subjects.</p