Analysis Of The Relationship Between MTHFR Gene Polymorphism And Cerebral Small Vessel Diseases

Objective:1.The association between methylenetetrahydrofolate reductase(MTHFR)gene polymorphism and hyperhomocysteinemia(HHcy)has been identified,and it is recognized as a risk factor of cerebrovascular disease.The distribution of C677 T polymorphism of MTHFR gene had regional and racial differences.The total frequency of C677 T allele in China was much higher than that in other countries,and the frequency of TT genotype and T allele in Hebei province was significantly higher than that in other provinces and cities.Therefore,the purpose of this study was to investigate the relationship between Cerebral small vessel diseases(CSVD),Large-vessel diseases(LVD)and MTHFR gene,homocysteine(Hcy)and other risk factors in the Han population in southern Hebei province.2.Essential hypertension is one of the pathogenesis of CSVD.Essential hypertension is often associated with HHcy(i.e.H-type hypertensive).HHcy increases oxidative stress and inflammatory response of vascular endothelial cells and damages endothelial cells.Endothelial injury is a key pathological process of CSVD.Therefore,this study investigated the correlation between essential hypertension,HHcy and CSVD in the Han population in southern Hebei province.3.The oxidative stress and inflammatory response were involved in the pathogenesis of CSVD.In the past,CSVD and dyslipidemia were studied as independent risk factors.In this study,we investigated the relationship between with the different parts of CSVD,different pathology and different severity of WML in the participants of oxidative stress in blood.The purpose of this study was to investigate whether there is a correlation between the participants in oxidative stress-Hcy,antioxidant component-UA,LDL,which plays the most important role in lipid metabolism and the different parts of CSVD,different pathology,different severity of WML.Methods: A retrospective study of 368 patients with non-cardiogenic ischemic stroke or transient ischemic attack in the Department of Neurology,second Hospital of Hebei Medical University.According to the 2015 Chinese consensus on diagnosis and treatment of cerebral small vascular diseases and TOAST classification,the patients were divided into two groups: LVD group and SVD group.The general condition(including sex,age,height,body weight,history of smoking and drinking,family history,etc.;previous history: hypertension,diabetes,coronary heart disease,hyperlipidemia,kidney disease,etc.)of all patients was collected.The results of post-hospital examination(including blood biochemistry,Hcy,glycosylated hemoglobin,liver and kidney function,blood lipid,etc.)and examination results(including head MRI+DWI+MRA,cervical artery ultrasound,cardiac examination,etc.)were recorded.PCR-restriction fragment length polymorphism(PCR-restriction fragment length polymorphism,RFLP)was used to identify the C677 T polymorphism of MTHFR gene.The risk factors related to the basic information of the two groups were analyzed;According to whether there was essential hypertension and high Hcy,the two groups were divided into three groups: H-type hypertension group,high Hcy group,simple hypertension group and normal blood pressure group;The association of different lesions location of CSVD(including anterior and posterior circulation),Fazekas scores,pathological classification including lacunar infarction(LI)and white matter lesions(WML)and the levels of Hcy,UA and LDL were discussed.Results:1.The overall MTHFR polymorphism of the patients with CSVD and LVD: in the Hardy-Weinberg equilibrium condition,the homozygote TT genotype in the MTHFR gene was 175(47.6%),166(45.1%)were CT-type heterozygotes,and 27(7.3%)were CC-type homozygotes.2.The polymorphism of the MTHFR gene C677 T is related to the plasma Hcy concentration: the polymorphism of the MTHFR gene C677 T is related to the plasma Hcy concentration: the plasma concentration of the CC genotype is 13.1±2.8 mmol/ L,the CT genotype is 14.1±7.9 mmol/ L,and the TT genotype is 21.1±15.9 mmol/ L(P<0.001).The distribution of the polymorphism was not directly related to the CVD group(P=0.513)or the LVD group(P=0.562),and there was no difference in the Hcy level in the two groups(P=0.867 and 0.900,respectively).3.Hypertension and diabetes mellitus were significantly correlated with the incidence of LVD: after adjusting the risk factors by non-conditional Logistic regression analysis,the LVD group was still associated with hypertension(odds ratio [OR] 1.666;95% confidence interval [CI] 1.048~ 2.647;P=0.031.),diabetes mellitus(odds ratio [OR] 1.578;95% confidence interval [CI] 1.012~2.459;P=0.044).4.The incidence of H-type hypertension group,high Hcy group,simple hypertension group and normal blood pressure group were compared.The order of occurrence in CSVD group was H-type hypertension group(51.9%)>simple high Hcy group(30.2%)>simple hypertension group(12.3%)>normal blood pressure group(5.6%).The order of occurrence in LVD group was H-type hypertension group(65.7%)> simple high Hcy group(23.7%)>simple hypertension group(8.6%)>normal blood pressure(7.0%).There was statistical significance(P< 0.05).5.In CSVD group,there was no association of MTHFR gene polymorphism with different sites(anterior and posterior circulation),Fazekas score and common pathological changes(mainly LI,WML).But the level of Hcy in LI(20.2 ±15.9 mmol/l)was significantly higher than that in WML(15.5 ±9.1mmol/L)(P<0.031).There was no significant difference in Hcy between anterior and posterior circulation and different Fazekas scores(P > 0.05).Besides,there was no significant difference in the levels of UA and LDL among all types(P > 0.05).Conclusions:1.In the population with acute stroke attack in southern Hebei Province,the expression rate of TT allele of MTHFR gene was significantly higher than that of normal population in Hebei Province,suggesting that TT mutation population was more likely to suffer from acute stroke.2.There was no significant difference in C677 T polymorphism and Hcy level between CSVD and LVD in this population,but this genetic effect was an important factor for the increase of Hcy,which may be related to region and race.3.The relationship between hypertension,diabetes mellitus and LVD was more closely than that of CSVD.4.Compared with WML,high level of Hcy was more correlated with LI,and had no correlation with UA and LDL.