medwireNews: Results of a Mendelian randomization analysis suggest a causal protective effect of serum iron against Parkinson's disease.
"These findings are important since evidence on the association between serum iron levels and [Parkinson's disease] risk collected so far has been controversial," say the researchers.
Epidemiologic studies have indicated a protective effect of iron against Parkinson's disease, but this conflicts with the previous assumption that iron has an adverse effect, based on the finding of increased iron levels in the substantia nigra and lateral globus pallidus of Parkinson's disease patients.
Mendelian randomization analyses take advantage of the random allocation of genes at conception to avoid the unmeasured confounding effects common to epidemiologic studies. For the current analysis, Cosetta Minelli (Imperial College London, UK) and team looked at the association between three genetic variants known to influence iron levels (HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791) and risk for Parkinson's disease.
"Since genotype influences on serum iron levels represent differences that generally persist throughout adult life, the estimate of our [Mendelian randomization] study reflects an effect of iron over the course of a lifetime," they write in PLoS Medicine.
Minelli et al drew the associations between the three variants and iron levels from a recent genome-wide meta-analysis of 21,567 people, and they show the association between the variants and Parkinson's disease using data on 20,809 Parkinson's disease patients and 88,892 controls from Europe or North America.
Based on the reported size and direction of the effect of the variants on iron levels, the team calculates that each 10 µg/dL increase in serum iron levels is associated with a 3% reduction in the risk for Parkinson's disease.
According to these figures, raising serum iron levels in Caucasians older than 60 years by one standard deviation (38 µg/dL) would reduce the number of Parkinson's disease cases from 100 to 88 per 10,000 people, say the researchers. They note that, in theory, associations detected in a Mendelian randomization analysis are causal.
"Similar large-scale [Mendelian randomization] studies investigating other markers of iron metabolism, such as ferritin and transferrin, could contribute to our understanding of the role of peripheral iron homeostasis in the pathophysiology of [Parkinson's disease]," say Minelli and team.
They add that further study of the pathophysiologic mechanisms are needed before the results can lead to recommendations for primary prevention.
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