title: TT genotype of the methylenetetrahydrofolate reductase C677T polymorphism is an important determinant for homocysteine levels in multi-ethnic Malaysian ischaemic stroke patients.
abstract: BACKGROUND
  The functional point mutation C677T in the methylenetetrahydrofolate reductase (MTHFR) gene, has been reported to contribute to hyperhomocysteinaemia which is a risk factor for atherothrombotic ischaemic strokes. This study evaluated the prevalence of the C677T polymorphism of the gene in Malaysian ischaemic stroke subjects of Malay, Chinese and Indian ethnicities, and its association with homocysteine levels (tHcy).
  
  
  METHODS
  A total of 292 subjects were recruited, comprising 150 ischaemic stroke patients and 142 control subjects who were age and sex matched. Plasma homocysteine, serum folate and vitamin B12 were measured in all subjects. Genotyping was carried out using PCR-RFLP.
  
  
  RESULTS
  The homocysteine levels were significantly higher (P = 0.001) in the stroke group (11.35 ± 2.75 μmol/L) compared to the control group (10.38 ± 2.79 μmol/L). The MTHFR C677T genotype distribution for the stroke group was 46%, 40% and 14%, respectively for CC, CT and TT genotypes and 59.9%, 33.8% and 6.3%, respectively for the control group. The genotype and allelic frequencies were significantly different between the 2 groups, with P = 0.02 and P = 0.004 respectively. No significant difference was seen in the genotype distribution inter-ethnically. An increasing tHcy was seen with every additional T allele, and the differences in the tHcy for the different genotypes were significant in both the control (P <0.001) and stroke groups (P <0.001).
  
  
  CONCLUSIONS
  This study shows that TT genotype of the methylenetetrahydrofolate reductase C677T polymorphic gene is an important determinant for homocysteine levels in Malaysian ischaemic stroke patients.
authors.affiliation: Department of Pharmacology, University of Malaya, Kuala Lumpur, Malaysia. elsa@um.edu.my
authors.forename: Elsa Haniffah
authors.initials: EH
authors.lastname: Mejia Mohamed
authors.forename: Kay Sin
authors.initials: KS
authors.lastname: Tan
authors.forename: Johari Mohd
authors.initials: JM
authors.lastname: Ali
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
mesh_terms: D002681:China / Q000208:ethnology; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood; D005787:Gene Frequency; D005838:Genotype; D006710:Homocysteine / Q000097:blood* / Q000235:genetics; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications; D007194:India / Q000208:ethnology; D008296:Malaysia; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D020521:Stroke / Q000097:blood* / Q000235:genetics*; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12