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Licensed Unlicensed Requires Authentication Published by De Gruyter June 1, 2005

Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic stroke

  • Larry Baum , Ka Sing Wong , Ho Keung Ng , Brian Tomlinson , Timothy Hudson Rainer , Daniel Kam Yin Chan , G. Neil Thomas , Xiangyan Chen , Peter Poon , Wing Sze Cheung and Kam Sang Woo

Abstract

The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene 677CT polymorphism causes an A222V amino acid change which affects MTHFR enzyme activity and can increase homocysteine, a vascular disease risk factor. This polymorphism was examined for association with stroke. In a case-control study of 241 ischemic stroke patients and 304 controls in Hong Kong, the V allele increased in stroke [28% vs. 20%, odds ratio (OR) 1.5, p=0.003]. A lack of significance for the increase in the VV genotype (7.5% vs. 4.6%, OR 1.7, p=0.16) may be due to its rarity in this region. V-allele carriers had more severe strokes (according to the NIH stroke scale). The association of the V allele with stroke occurred mostly in women or older subjects and was due to decreasing V allele frequency with age, as seen in other studies. This V frequency decline with age might be due to a loss of V-carrying controls from a higher risk of cancer, vascular disease, bone fracture, and kidney failure when folate is sparse. Examination of previous studies revealed that the association of VV genotype with stroke appeared stronger in Japan than elsewhere, possibly due to dietary differences. Perhaps folate supplementation for stroke prevention would particularly benefit VV individuals in such high-risk regions.


Corresponding author: Larry Baum, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong, PR China Phone: +852-26323146, Fax: +852-26373852,

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Received: 2004-7-13
Accepted: 2004-8-27
Published Online: 2005-6-1
Published in Print: 2004-12-1

©2004 by Walter de Gruyter Berlin New York

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