People with high concentrations of homocysteine, an amino acid in the blood, may have an increased risk of stroke, suggests a study published in this week’s issue of The Lancet.
Stroke is the third most common cause of death in developed countries. There are 125,000 cases of stroke in the UK each year and 60,000 deaths. Because treatment is limited, prevention through modification of risk factors such as high blood pressure and smoking is important.
Observational studies measuring homocysteine concentrations in healthy individuals have found that, on average, those with high levels of homocysteine in their blood are more likely to have a stroke. But other factors that increase homocysteine concentration and stroke risk— such as smoking and socioeconomic class—may be responsible for the relationship observed in these studies, confounding the result.
Uncovering whether or not homocysteine concentration is linked to stroke is important because folic acid and B vitamins can lower its concentration, although the results of large randomised trials to examine the efficacy and safety of this approach are still awaited.
Aroon Hingorani (University College London, UK) and colleagues used an approach known as Mendelian randomisation to overcome some of the problems of confounding factors seen in observational studies. The investigators analysed published data on the association between stroke and common variation in a gene called MTHFR, which is known to influence homocysteine concentration. People randomly inherit variant (TT) of the gene, which gives them a higher concentration of blood homocysteine, or variant (CC), which results in lower levels of the amino acid in their blood.
The authors compared risk estimates from observational studies of homocysteine and stroke with those obtained from genetic studies of MTHFR and stroke. They found individuals who carried the TT genotype of MTHFR had, on average, both a higher concentration of homocysteine, and a small increase in the risk of stroke. The effect of the variant on stroke risk was close to that expected from its effect on homocysteine concentration.
Dr Hingorani comments: “Because of the random allocation of the gene variant in advance of disease development this concordance of risk estimates implies that the relation between homocysteine and stroke seen in observational studies is not substantially confounded by other factors. Our study therefore provides evidence for a role of homocysteine in the development of stroke, though it must be emphasized that a systematic review of published studies such as this might be affected to some degree by reporting bias.