Association of acute ischemic stroke with the MTHFR C677T polymorphism but not with NOS3 gene polymorphisms in a Singapore population


Dr Kyaw Thu Moe, Research and Development Unit, National Heart Centre, Singapore, Singapore (tel.: 65 63214282; fax: 65 63213606; e-mail:


Background and purpose:  The association of polymorphisms in the nitric oxide synthase 3 (NOS3) gene (T-786C, variable number tandem repeats 4A/B/C, and G894T) and in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) with acute ischemic stroke have been reported.

Methods:  First-time onset acute ischemic stroke patients (n = 120) and controls (n = 207) with no past history of stroke were compared. Allele specific gene amplification and restriction fragment length polymorphism (RFLP) analysis were used to determine the genotype and allelic frequencies in both groups. Plasma homocysteine (Hcy) and nitrite levels were measured.

Results:  No significant association of NOS3 polymorphisms with ischemic stroke was noted. The TT genotype of the MTHFR C677T polymorphism was significantly associated with ischemic stroke (= 0.004). Elevated plasma Hcy levels were also significantly associated with ischemic stroke (= 0.001).

Conclusions:  The TT genotype of C677T polymorphism in the MTHFR gene contributes to genetic susceptibility of acute ischemic stroke in a Singapore population.