The Correlation Of Homocyteine Concentration And MTHFR Gene Polymorphism With Ischemic Stroke

Setting and objectiveIschemic stroke (IS), also known as cerebral infarct, is a most commoncerebrovascular disease (CVD), accounting for about75%. Owing to its highincidence, disability, recurrence rate, and mortality, IS has been one of the majorcausing serious harm to human and costing most health resources in differentcountries. The known factors, such as hypertension, diabetes mellitus, hyperlipidemia,smoking, drinking, obesity, asymptomatic carotid artery stenosis，atrial fibrillationand other heart disease etc. cannot fully illustrate the occurrence and development ofIS. In1969, MeCully proposed that hyperhomocysteinemia was possibly associatedwith atherosclerosis. Since then, scholars world widely have carried out lots ofclinical studies on this point of view. Recently, research results have demonstratedthat hyperhomocysteinemia is closely related to the occurrence and development ofIS. The metabolization of Hcy relies on folic acid, vitamin B12, N5, andmethylenetetrahydrofolate reductase (MTHFR). MTHFR, as the key enzyme in themetabolization, its base mutation results in the absence and inactivity of MTHFR.Thereinto, C677T base mutation occurs most commonly. Furthermore, either activitydecline of MTHFR or the absence of folic acid and vitamin B12leads to the happen of hyperhomocysteinemia. The research tested the Hcy, folic acid, and vitamin B12levels in plasma and the polymorphism of MTHFR gene to reveal the correlation ofHcy and the MTHFR gene polymorphism with IS.MethodsThe research established a case group and a control one consisting of85ISpatients and82people, respectively. The circulating enzymatic method was employedto test the Hcy concentration in plasma. People with an Hcy concentration higher than15μmol/L were diagnosed as hyperhomocysteinemia patients. The folic acid andvitamin B12levels were measured using immunoassay method. And the PolymeraseChain Reaction–Deoxyribonucleic Acid Microarray(PCR-DNA Microarray) was usedto analyze the polymorphism of MTHFR gene.ResultsThe Hcy concentration (16.75±3.58μmol/L) in plasma of IS group is apparentlyhigher than that of the control group (10.06±3.01μmol/L)(p<0.001).Correspondingly, the numbers of hyperhomocysteinemia patients in IS and thecontrol groups are34and6which account for40.0%and7.32%,he difference presents remarkably statistical significance (2=29.82, p<0.001).Regarding folic acid and vitamin B12levels, the control group is higher than the ISone (P<0.001). The Hcy of the two groups is negatively correlated with the folic acidlevel; the correlation coefficients of IS and control groups are （r=-0.41，p<0.01）and（r=-0.23，p<0.05）respectively. Similarly, the Hcy is negative correlated with thevitamin B12levels as well; and the correlation coefficients are（r=-0.34，p<0.01）and（r=-0.21，p<0.05）respectively. Moreover, the Hcy in the plasma of MTHFR geneTT homozygote group exceeds that of CT heterozygote and CC homozygote groups(p<0.01); and there is difference between the Hcys of CT heterozygote and CChomozygote groups (p<0.01); the distribution frequency of TT homozygote ofMTHFR gene on IS is higher than that of the control group (p<0.01); the frequenciesof T and C alleles of MTHFR gene are57.65%and42.35%, respectively; while forthe control group, they are38.41%and61.59%. Obviously, there is differencebetween the two groups (2=12.37, p<0.01).Conclusions An increase of Hcy concentration in plasma is one of the risk factors of IS. Hcyis negatively correlated with folic acid and vitamin B12levels; the absence of folicacid and vitamin B12is possibly the major cause of a high Hcy concentration.Meanwhile, the increasing Hcy is probably resulted from the MTHFR gene mutation.The C677T mutation of MTHFR gene may be closely related to the susceptibility ofIS.