title: Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic stroke.
abstract: The 5,10-methylenetetrahydrofolate reductase ( MTHFR ) gene 677C --> T 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.
authors.affiliation: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong, PR China. iwbaum@cuhk.edu.hk
authors.forename: Larry
authors.initials: L
authors.lastname: Baum
authors.forename: Ka Sing
authors.initials: KS
authors.lastname: Wong
authors.forename: Ho Keung
authors.initials: HK
authors.lastname: Ng
authors.forename: Brian
authors.initials: B
authors.lastname: Tomlinson
authors.forename: Timothy Hudson
authors.initials: TH
authors.lastname: Rainer
authors.forename: Daniel Kam Yin
authors.initials: DK
authors.lastname: Chan
authors.forename: G Neil
authors.initials: GN
authors.lastname: Thomas
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Chen
authors.forename: Peter
authors.initials: P
authors.lastname: Poon
authors.forename: Wing Sze
authors.initials: WS
authors.lastname: Cheung
authors.forename: Kam Sang
authors.initials: KS
authors.lastname: Woo
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002545:Brain Ischemia / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000378:metabolism; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017678:Sex Distribution; D012737:Sex Factors; D020521:Stroke / Q000201:enzymology* / Q000235:genetics*
chemical_list: D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)