| [Background and Objective]White matter lesions(WML)are common cerebrovascular diseases.WML mainly causes cognitive impairment,speech disorders,mental disorders,gait disorders,urination disorders,etc,which seriously affect the health and quality of life of patients.WML was often detected on brain MRI in the elderly,and WML was closely associated with the increased risk of stroke and dementia.The risk factors and pathogenesis of WML are not clear.WHL can be caused by a variety of factors including damage to small blood vessel walls,ischemia,micro-hemorrhages.The pathogenesis of WML is closely related to endothelial cell injury.It is found that homocysteine is an independent risk factor of ischemic cerebrovascular disease.HHcy can lead to dysfunction of vascular endothelial cells through oxidative stress,destruction of elastic layer and collagen fiber of cerebral vascular wall.However,there are few studies on the pathogenesis and mechanism of Hcy and WML,which need to be further clarified.Breaches of the barrier between the cerebrospinal fluid and the brain,gliosis,or loss and deformation of the myelin sheath are possibly another cause of WML.The mechanism of WML is not clear,may associated with breakdown of the blood-brain barrier(BBB).BBB breakdown lead to increased permeability,and blood components penetrate into the parenchyma and perivascular tissue,resulted in damage of neurons and glial cells,which was another important mechanism of WML.In recent years,evidence showed that hemostatic factors play an important role in the development of WML.Fibrinogen(FIB)was one of the main coagulation factors,which can be used as an important determinant in the process of thrombosis.After BBB breakdown,FIB entered the parenchyma of the brain and formed fibrin,which lead to cognitive dysfunction.The relationship between FIB and WML has not been clarified,and it needed to be further clarified.In recent years,genetic characteristics and mechanisms of WML have been studied,some monogenic causes have been found,and some studies have shown that genetic factors play a certain role in the pathogenesis and progression of WML.The study of the risk factors and genetic basis of WML contributes to the early diagnosis and treatment of WML.Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in the metabolic pathway of Hey in human body.The mutation of some polypeptide sites can lead to the decrease of activity of the enzyme,cause Hey metabolic disorder and lead to hyperhomocysteinemia.The most common mutation in MTHFR gene is C677T mutation.The β-fibrinogen gene(FGB)was the speed limiting step of FIB synthesis,and the FGB 455G-A mutation corresponded to the increase of plasma FIB level.Meta analysis showed that FGB-455G/A polymorphism is closely related to cerebral infarction and was a susceptible marker for ischemic stroke in Chinese population.This study was to explore:1)The risk factors of WML;the relationship between plasma Hey level and WML;the relationship between plasma FIB level and WML;2)The relationship between the MTHFR gene C677T polymorphism and the level of plasma Hey;the association between MTHFR gene C677T polymorphism and WML in Chinese Han population;3)The association between the FGB-455G/A polymorphism and WML in Chinese Han population,and analyze the possible pathogenesis of WML.[Methods]1.Study about risk factors of WML.A case control study was used to collect 188 hospitalized patients(no blood relationship between the research object)in the department of Neurology,the Second Hospital of LianyungangCity from Oct.2014 to Dec.2015.The modified Scheltens scale was used to evaluate the WML score of the brain MRI of all the subjects who were enrolled in the group.According to the MRI results,the subjects were divided into the WML group and the control group.The level of plasma Hey was detected by circulating enzyme.FIB and other laboratory indicators detected in this study.2.Association of MTHFR gene C677T polymorphism with WML.The cases involved are those of study about risk factors of WML.MTHFR gene C677T polymorphism was analyzed by Taqman probe.3.Association of p-fibrinogen gene 455G/A polymorphism with WML.The patients(n=269,no blood relationship)were chosen from Oct.2014 to Mar.2016 in our hospital as the research object in the Second Hospital of LianyungangCity.Modified Scheltens scale was used to score the degree of white matter lesions with MRI,according to MRI were divided into WML group and control group.FGB gene 455G/A polymorphism was analyzed by polymerase chain reaction.Analysis of the relationship between FIB and WML was performed by multiple factor Logistic regression.[Results]1.Study about risk factors of WML.1)A total of 104 patients in WML group were collected,including 60 males and 44 females,the mean age was 68.05±9.22.There were 74 cases in the control group,including 43 males and 31 females,the mean age was 58.47±9.32.The proportion of hyperhomocysteinaemia was 89(85.6%)in WML group were significantly higher than 40 cases(54.1%)in control group.The plasma Hcy level and FIB in WML group was[16.81 umol/L(11.33,18.92)],3.18±0.87g/L were significantly higher than those in control group[11.40μmol/L(8.28,14.23)],2.77±0.58 g/L the differences were statistically significant(P<0.01).2)Compared with the control group,WML group had no statistical significance in gender,smoking history,diabetes,coronary heart disease and hyperlipidemia(P>0.05),there was a significant difference in age,hypertension,Hcy and fibrinogen level(P<0.01).Multiple factors logistic regression analysis of showed age,hypertension,HHcy and high fibrinogen level were independent risk factors for WML.2.Association of MTHFR gene C677T polymorphism with WML.1)TT,CT and CC genotypes were used to compare the plasma Hcy level in each group.The highest level in TT group was(mean 18.37μmol/L),followed by CT group(mean 16.02μmol/L),and CC group was the lowest(mean 13.55μmol/L),the difference was statistically significant(P=0.026).2)The two genotype distributions were all consistent with the Hardy-Weinberg equilibrium law.There was no significant difference in the frequency distribution of MTHFR C677T genotype between the two groups(P=0.534).Compared with the control group,there was no significant difference in T allele frequency between the two groups(P=0304).3.Association of β-fibrinogen gene 455G/A polymorphism with WML.1)A total of 269 patients were enrolled in this study,mean age was 63.89±9.58 years.There were 177 cases in WML group,including 98 males and 79 females,mean age was 66.16±9.12 years.92 cases in control group,including 51 male and 41 female,mean age was 59.54±8.95 years.2)The FIB levels of GG,GA and AA genotypes were compared.We found that AA group had highest fibrinogen levels(4.30±0.79g/L),followed by GA group(3.95±0.65g/L),while GG group had lowest levels(3.71±0.58g/L).The differences among the AA+GA groups and GG group were statistically significant(P=0.005).3)The distribution of genotypes in the two groups accorded with the law of Hardy-Weinberg equilibrium.FGB-455 GG,GA,AA genotype frequencies in WML group were 50.6%,41.7%,7.7%,control group were 61.5%,35.2%,3.3%.G,A allele frequency in WML group was 71.5%and 28.5%,in control group were 79.1%and 20.9%.Genotype and allele frequency differences in two groups were not statistically significant(P>0.05).[Conclusion]1.Age,hypertension,HHcy and high fibrinogen level were independent risk factors for white matter lesions.2.The levels of plasma homocysteine and FIB were positively correlated with white matter lesions.3.MTHFR gene C677T mutation was significantly correlated with the plasma homocysteine levels.4.There was no significant correlation between the white matter lesions and the MTHFR gene C677T mutation.5.FGB-455G/A polymorphism is related to the level of plasma FIB,and the G-A mutation increases the level of plasma FIB.6.There was no significant correlation between the FGB-455G/A polymorphism and WML in Chinese Han population. |
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