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To the Editor:The recent meta-analysis of Cronin et al1 examined the association between the MTHFR C677T polymorphism, the strongest genetic determinant of moderate hyperhomocysteinemia, and ischemic stroke. These authors considered 31 studies, including 15 from Europe, and concluded for the existence of an overall weak and dose allele-dependent association; in the European area, they reported a lack of association between the MTHFR C677T polymorphism and ischemic stroke in Northern and Central Europe, whereas the MTHFR C677T polymorphism was surprisingly a significant risk factor for ischemic stroke in Italy. The same authors1 suggested that it was important to investigate whether this finding was attributable to population differences in T allele frequency, folate status, or other genetic or environmental influences. In fact, the frequency of MTHFR 677T allele is higher in Italy than in Central and Northern Europe, and the same gradient is observed for the dietary intake and status of folate.2 Therefore, the significant association observed by Cronin et al1 in Italy should be regarded as paradoxical if one …

Heterogeneity of Association Between MTHFR and Stroke Among European Regions: Additional Population Studies Are Needed in Italy