Association Between High Homocysteine, MTHFR C677T Polymorphism And Acute Ischemic Stroke Subtypes According To TOAST Classification

Objective : To observe the correlation of hyperhomocysteinemia(HHcy) and acute ischemic stroke(AIS).To analyze the effect of methylenetetrahydrofolate reductase(MTHFR) C677 T polymorphism to plasma homocysteine(Hcy) levels.To determine the role of MTHFR C677 T polymorphism in acute ischemic stroke.All the cases were divided to different subtypes according to TOAST classification.To investigate the relationship between plasma homocysteine levels and ischemic stroke due to large and small artery diseases.At the same time,we investigated the relationship between MTHFR C677 T polymorphism and large artery atheroscelerosis(LAA)as well as small artery occlusion(SAO).Methods:1. 146 subjects included consecutive cases of acute ischemic stroke attending the Second Affiliated Hospital to Nanchang University from November2013 to April 2014,enrolled in this study.All cases were admitted to the hospital within onset time less than 7 days. The control group contained of 80 healthy subjects whose gender and age were macthed with the patients.All subjects were extracted fasting vein blood 2ml the next morning. Hcy were assayed by rate method.All cases were difined according to TOAST classification.80 cases were included in the LAA group and 38 in SAO group. 2.Hcy levels were compared among AIS(LAA +SAO),LAA,SAO and the control group. 3.We analysed the correlation between Hcy and age,Gender,serum folate,serum vitamin B12 and creatine, respectively. 4. 2*2ml EDTA tubes of fasting vein blood were extracted from all subjects the next morning to test the frequency of MTHFR C677 T genotypes and alleles.The obtaind blood was kept in 4 centigrade until received by genetic- testing company.We compared the distribution of genotypes and alles among AIS,LAA,SAO and control group.We also compared the Hcy levels among genotypes of TT,CT and CC. Risk factors of AIS and LAA and SAO were selected by logistic regression analysis.Results:1.When compared to control group,plasma Hcy levels in AIS group LAA group and SAO group were significantly higher than that in the control group(P< 0.05).Plasma Hcy levels in SAO group was also higher than that in the LAAgroup,but the difference was not statistically significant(P>0.05).2.Differences in frequency of genotypes and alles in AIS group and LAA group were not statistically significant when compared to the control group,respectively(P>0.05).The frequency of TT genotype as well as T allele in SAO was higer than those in both LAA and the control group(P < 0.05).3.Plasma Hcy concentrations in TT and CT genotype group were higher than that in CC group,respectively(P<0.05).Hcy levels in TT genotype group was also higher than that in CT group(P<0.05).4.Plasma Hcy levels in male subjects was higher than that in female(P < 0.05).Age,serum FA,VB12,Cr were corelated with Hcy(r value was 0.245、-0.508、-0.385、0.337 respectively, P < 0.05) by Linear regression analysis. Using logistic regression analysis,we found that hypertensive and HHcy were independent risk factors for AIS,LAA and SAO;Diabetes was an independent risk factos for AIS and LAA.Conclusion:1.HHcy is an independent risk factor for AIS.It has influence on both LAA and SAO.2.MTHFR C677 T polymorphism does not corelates with AIS directly,it is not the genetic risk factor for AIS.However,it is a probable genetic risk factor for SAO.3.T allele of the 677 th site of MTHFR gene will elevate plasma Hcy levels,laking of FA and VB12,increased serum levels of creatine,male gender,aging were related to HHcy.