Relationship Between The Homocysteine Levels And MTHFR C677T Gene Polymorphisms And Cerebral Artery Atherosclerotic Stenosis In The Patients With Ischemic Stroke

Objective:To investigate the relationship between plasma homocysteinemia levels,gene polymorphisms of methylenetetrahydrofolate reductase(MTHFR)and stenosis of intracranial and extracranial artery.Methods: In a retrospective case-control study, we collected patients with ischemic cerebrovascular disease 126 cases,according to the presence of cerebral vascular stenosis divided into 91 cases of cerebral vascular stenosis and 35 cases non-stenosis. The stenosis group were divided into simple extracranial stenosis group(30 cases), simple intracranial stenosis group(61 cases) according to stenosis location.The plasma HCY levels were measured by fluorescence poparization immunoassay(FPIA),MTHFR C677 T gene polyorphisms were ananlyed PCR and restriction fragment length polymorphism(PCR-RFLP).Results:1.Median of plasma HCY concetration level was significantly higher in patients with stenosis of cerebral artery[M、IRQ:(14.88(12.89-17.86)umol/L]than that no-stenosis group[M、IRQ:11.3(9.8-13.6)umol/L](P<0.05);the HCY levels of intracranial stenosis group[M、IRQ:15.65(13.7-17.84)umol/L]and extracranial stenosis group[M、IRQ:15.69(12.7-18.64)umol/L]than higher that no-stenosis group,but HCY levels between in stenosis were not significantly different(p>0.05).2.In cerebral artery stenosis group and no-stenosis group,medians of HCY concentration level of TT genotype with MTHFR 677C→T gene mutation were respectively[M、IRQ:18.72(17.3-22.13)umol/L]、[M、IRQ:15.1(13.2-25.90)umol/L],which were significantly higer than those of CC genotype, respectively[M、IRQ:14.61(13.07-16.67)umol/L]、[M、IRQ:10.7(9.8-13.2)umol/L](P<0.05).There were no significant differences of frequency of homozygote TT and mutantT allels among intracranial stenosis group,extracranial stenosis group and no-stenosis group(P>0.05).3.Multi-variable logistic regression analysis showed that hyperhomocysteinemia(HHCY) is a risk factor for the cerebral artery stenosis[( odds ratio,OR) 6.054,95%( confidence interval,CI)1.958-18.725;P=0.002];Futher study shows hyperhomocysteinemia(HHCY) is a risk factor for the intracranial and extracranial artery stenosis.The odds ratio( OR)and95% confidence interval(CI) are [OR 8.623,95%CI2.466-30.153;P=0.001][OR 5.198,95%CI 1.356-19.993;P=0.016].There were no definite correlation between MTHFR677C→T genotype and cerebral artery stenosis.Conclusion: Hyperhomocysteinemia is a risk factor of the cerebral artery stenosis,including extracranial and intracranial artery stenosin.there is no correlation between the MTHFR 677C→T genotype and cerebral artery stenosis.MTHFR677C→T genotype mutation is the most important determinant of HCY levels,but nor definitely related to the distribution of stenosis of intracranial and extracranial artery.