Early-onset ischaemic stroke: Analysis of 58 polymorphisms in 17 genes involved in methionine metabolism
- 1 January 2010
- journal article
- Published by Georg Thieme Verlag KG in Thrombosis and Haemostasis
- Vol. 104 (08), 231-242
- https://doi.org/10.1160/th09-11-0748
Abstract
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.Funding Information
- Italian Ministry of Health ((RBLA038RMA_008))
This publication has 21 references indexed in Scilit:
- Mechanisms of homocysteine toxicity in humansAmino Acids, 2007
- Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidenceBMJ, 2006
- Mining literature for a comprehensive pathway analysis: A case study for retrieval of homocysteine related genes for genetic and epigenetic studiesLipids in Health and Disease, 2006
- Genetic Determinants of Plasma Total HomocysteineSeminars in Vascular Medicine, 2005
- Homocysteine and thrombosis: from basic science to clinical evidenceThrombosis and Haemostasis, 2005
- Genetics of hyperhomocysteinaemia in cardiovascular diseaseAnnals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2003
- Homocysteine and cardiovascular disease: evidence on causality from a meta-analysisBMJ, 2002
- A Second Genetic Polymorphism in Methylenetetrahydrofolate Reductase (MTHFR) Associated with Decreased Enzyme ActivityMolecular Genetics and Metabolism, 1998
- Plasma Homocysteine Levels and Mortality in Patients with Coronary Artery DiseaseThe New England Journal of Medicine, 1997
- A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductaseNature Genetics, 1995