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Folate and Stroke Risk

A stroke can be frightening, debilitating, and sometimes deadly. Strokes are complicated events caused by a variety of contributing factors, including genetics and environment. One potential factor is an elevated level of homocysteine in blood plasma. Homocysteine is a chemical created by the breakdown of an amino acid called methionine.

Though a causal relationship hasn’t yet been proven, it’s thought that elevated homocysteine levels can irritate and harden blood vessels. Even moderately elevated levels of homocysteine in blood plasma are associated with increased risk of stroke and other vascular problems. There’s some evidence suggesting that folate has a protective effect against stroke and vascular disease, and its role in regulating homocysteine levels may be the reason. Reduced Folate Carrier (RFC), a cellular transport system that delivers folates to cells, is crucial to the body’s ability to regulate homocysteine.

Medical researchers in South Korea recently conducted a study that looked for a relationship between RFC function and stroke. They examined three variants, or minor alleles, in the gene sequence affecting RFC function, and how they correlate with folate levels, homocysteine levels, and occurrence of stroke in 1,442 participants, including over 850 stroke patients and 500 control subjects with no recent history of stroke or heart attack. Stroke patients were broken into two groups. Ischemic stroke patients experienced strokes caused by a clot or arterial blockage in the brain, as opposed to another region of the body, such as the heart. The second group of stroke patients had suffered “silent strokes” – symptomless brain injuries usually caused by blood clots. Silent strokes are often precursors to more damaging stroke events.

After obtaining DNA samples from the participants and screening them for the three gene variants of interest, researchers found that one particular variant, RFC-1 80G (where the “G” is substituted in the place of an “A”), was found significantly more frequently in both stroke groups than in the control subjects. This result suggests that the variant is an important risk factor for stroke, possibly due to an influence on folate levels. The current study, which is consistent with previous research, suggests that the RFC-1 80G allele is related to low plasma folate levels. Other studies have also found this same substitution to be associated with neural tube defects, congenital heart defects, and even some cancers.

Overall, the three variants examined in the study occurred significantly more often in stroke patients than in control subjects. The variants were associated with elevated levels of homocysteine and folate deficiency in ischemic stroke patients, as well as some of the silent stroke patients. This suggests that they somehow influence homocysteine and folate levels, though researchers don’t know how yet.

The study has raised other unanswered questions. For reasons yet unknown, strong associations between homocysteine and folate levels were more often found among women than men. The study also suggests that all three RFC-1 variants are associated with blockages of small blood vessels, but not other types of blood vessels.

Overall, the study suggests that the RFC-1 variants affect plasma levels of homocysteine and folate, contributing to risk of ischemic stroke and silent stroke. In the future, looking for these variants may help medical practitioners assess patients’ stroke risk.

The study, published in the online journal PLoS One in February 2015, is publicly available online.

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Carolyn Ledowsky

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