Association of hyperhomocysteinemia and methylenetetrahydrofolate reductase gene polymorphisms with ischemic stroke in Northwest Chinese population / 中国组织工程研究

ABSTRACT

BACKGROUND: It is proposed that elevated serum homocysteine is an important independent risk factor for ischemic stroke (IS), and 5, 10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for homocysteine metabolism. The relationship between genetic mutation of MTHFR and IS remains controversial.OBJECTIVE: To examine the association of hyperhomocysteinemia and two MTHFR gene polymorphisms with IS in Northwest Chinese population.DESIGN: Case-control study.SETTING: Department of Neurology, First Hospital Affiliated to Jilin University, and Department of Neurology, Xijing Hospital, Fourth Military Medical University of Chinese PLA.PARTICIPANTS: Ninety-seven consecutive patients with ischemic stroke (71 males and 26 females) treated between November 2001 and May 2002were recruited, who were diagnosed by CT scan or MRI in the Department of Neurology, Xijing Hospital, Fourth Military Medical University of Chinese PLA. The control group consisted of 94 subjects (58 males and 36 females) without history of ischemic stroke. All the subjects were free of intracranial hemorrhage, cancer, renal dysfunction, and none used multivitamins or estrogen.METHODS: Serum homocysteine was measured by fluorescence polarization immunoassay. Polymerase chain reaction-restriction length polymorphism (PCR-RFLP) method was employed to detect the genotype at the two sites of C677T and A1298C in MTHFR gene.MAIN OUTCOME MEASURES: Serum homocysteine levels and the genotypic frequency frequencies of the two mutations of MTHFR.RESULTS: The 677T allele frequency was 59.3% in IS patients and 44.7% in the controls, showing significant differences (P=0.006), but no difference in 1298C allele frequency was detected between the two groups (22.7% vs 19.7%, P ＞ 0.05). Homozygous 677TT genotype was closely associated with hyperhomocysteinemie (P ＜ 0.01). In multivariate logistic regression analysis,677T gene mutation and hyperhomocysteinemie were all associated with the IS, with an OR of 1.870 and 1.031 (P＜ 0.05), respectively.CONCLUSION: Hyperhomocysteinemie is a risk factor of IS, and C677T mutation significantly increases homocysteine levels, and serves also as an independent genetic risk factor of IS.