• Vol. 40 No. 4, 186–191
  • 15 April 2011

TT Genotype of the Methylenetetrahydrofolate Reductase C677T Polymorphism is an Important Determinant for Homocysteine Levels in Multi-Ethnic Malaysian Ischaemic Stroke Patients



Introduction: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).

Materials and 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).

Conclusion: 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

Stroke is the major cause of adult disability in developing countries. Traditional risk factors contribute up to 69% of the total risk of ischaemic stroke. There is a substantial body of knowledge to suggest that there are novel risk factors which may confer additional risks. Hyperhomocysteinaemia (hyperHcy) has been identified as a potentially modifiable risk factor for stroke. Homocysteine (Hcy) has also been shown to be atherogenic and thrombogenic in experimental models. The 5,10-methelenetetrahydrofolate reductase (MTHFR) is an important enzyme which regulates plasma homocysteine levels. A C677T point mutation (p.A222V) has been linked to increased risk for ischaemic stroke in various population studies, but no systematic study has been done in the Malaysian population. The MTHFR gene is located at 1p36.3, consisting of 11 exons with the polymorphism occuring at exon 4. The aim of this study is to investigate if there is an association between Hcy and MTHFR C677T polymorphism in the multi-ethnic Malaysian ischaemic stroke patients.

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