Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic stroke.
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.
Baum
Larry
L
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong, PR China. iwbaum@cuhk.edu.hk
Wong
Ka Sing
KS
Ng
Ho Keung
HK
Tomlinson
Brian
B
Rainer
Timothy Hudson
TH
Chan
Daniel Kam Yin
DK
Thomas
G Neil
GN
Chen
Xiangyan
X
Poon
Peter
P
Cheung
Wing Sze
WS
Woo
Kam Sang
KS
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*
D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)