Early-onset ischaemic stroke: analysis of 58 polymorphisms in 17 genes involved in methionine metabolism.
The hypothesis underlying this study is that variations in genes involved in methionine metabolism may contribute to genetic susceptibility for early-onset ischaemic stroke. We investigated 58 polymorphisms in AHCY, BHMT, BHMT2, CBS, ENOSF1, FOLH1, MTHFD1, MTHFR, MTR, MTRR, NNMT, PON1, PON2, SLC19A1, SHMT1, TCN2, TYMS genes on genomic DNA from 501 young patients who survived ischaemic stroke and 1,211 sex and age comparable controls. Genotype distribution was significantly different between patients and controls for the following SNPs: rs10037045 BHMT, rs682985 BHMT2, rs1051319 CBS, rs202680 FOLH1, rs2274976 MTHFR, rs1979277 SHMT1, rs20721958 TCN2. On multiple logistic regression analysis adjusted for traditional risk factors, rs10037045 BHMT, rs682985 BHMT2, rs1051319 CBS, and rs202680 FOLH1 remained independent risk factors for stroke. After haplotype reconstruction, generalised linear model analyses adjusted for traditional risk factors and using the FDR multiple testing correction showed significant associations between ischaemic stroke and BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS haplotypes. This study identifies significant genetic associations between premature ischaemic stroke and haplotypes in BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS genes involved in methionine metabolism.
Giusti
Betti
B
Department of Medical and Surgical Critical Care, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. betti.giusti@unifi.it
Saracini
Claudia
C
Bolli
Paola
P
Magi
Alberto
A
Martinelli
Ida
I
Peyvandi
Flora
F
Rasura
Maurizia
M
Volpe
Massimo
M
Lotta
Luca A
LA
Rubattu
Speranza
S
Mannucci
Pier Mannuccio
PM
Abbate
Rosanna
R
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008715:Methionine / Q000378:metabolism*; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D006710:Homocysteine; D008715:Methionine