The Correlation Study Of Methylenetetrahydrofolate Reductase(MTHFR)Gene 677 C/T Polymorphism And Serum Homocysteine(HCY)level With Coronary Heart Disease

Introduction 1.Background Methylenetetrahydrofolate reductase(MTHFR)is the key enzyme in the metabolize process of Homocysteine(HCY).The MTHFR gene located at 1p363,with 11 exons.A lot of mutation have been reported and the C677 T mutation is the most common.The C677 T mutation can produce a Hinf? restriction enzyme's recognition site,which will replace the Ala with Val.As result,the activity of MTHFR was decreased and the remethylation progress of HCY was inhibited which will lead to hyperhomocystinemia at last.The level of HCY in blood is influenced by many factors,such as inheritance,environment and nutrition.However,the mutation of MTHFR is the main factor in hyperhomocystinemia after removing those external factors.HCY is also cytotoxicity,producing peroxidation in metabolic process,which can cause apoptosis.2.Progress Cardiocerebral vascular disease is one of the high actual diseases,especially CHD and cerebral infarction.Many researchers focus on the inheritance,especially lipid metabolism.More and more studies indicate that the high level of serum HCY correlates with arteriosclerosis(AS)diseases.Recent studies show that hyperhomocystinemia is a new independent risk factor.At present,N5,N10-MTHFR gene is the main candidate while study cardiocerebral vascular diseases.The influence of MTHFR polymorphism in cerebral arterial thrombosis has also been wide concerned.MTHFR gene plays an important role in folate metabolism as well,the mutation ofMTHFR gene decrease the enzyme's activity and induce cardiac malformation at last.Many studies report that the genetype of T/T is 3.437 times than the genetype of C/C and C/T in inducing congenital heart disease.It has been discovered that the mutation of MTHFR gene is highly correlated with the level of folic acid and serum HCY,which is related to coronary disease and depression.Primary hypertension is an independent risk factor in cardiovascular diseases and the level of serum folic acid and HCY are the independent risk factors as well.At the same time,the mutation of MTHFR gene can also lead to pregnancy-induced hypertension syndrome.Pregnant women with MTHFR mutation are more likely to suffer from hyperhomocysteinemia.3.Goal In summary,the mutation of MTHFR gene and the level of serum HCY are correlated with many diseases,which raise the researchers' concerns.However,studies in the mutation of MTHFR gene and the level of serum HCY in AS and coronary disease are not enough with inconsistent conclusion.We consider that the mutation of MTHFR gene and the level of serum HCY in CHD,especially different types of CHD and CHD complicated with different diseases,in order to evaluate whether hyperhomocystinemia is the independent risk factor or not.Furthermore,we can measure the mutation of MTHFR gene and the level of serum HCY to help detecting and predicting CHD.Objective and methods 1.Sampling The mutation of MTHFR gene and the level of serum HCY correlate with many diseases,and the sampling process should remove the influence factors from congenital heart disease,myocardiopathy,valvular heart disease,pregnancy,liver and kidney dysfunction.And the control group includes the non-CHD patients without congenital heart disease,hypertension,myocardiopathy,valvular heart disease,stroke,pregnancy,liver and kidney dysfunction.2.MTHFR detection Collect venous blood samples.DNA was extracted by TIANGEN's kit.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and fluorescent PCR were performed in detecting MTHFR genetypes.3.Subgroups The patients were divided into CHD group and control group.In CHD group,the patients were divided into ACS group and stable angina group.Meanwhile,CHD patients were divided into two subgroups whether complicated with hypertension or not and whether complicated with hyperlipidemia or not.Results There are significant differences in the level of serum HCY between CHD group and control group(P<0.05).Odds ratio analysis discovers that C/T type(OR: 5.53,95%CI: 3.48-8.80,P:<0.05);T/T type(OR: 7.69,95%CI: 3.89-15.20,P:<0.05)and C/T+T/T type(OR: 6.06,95%CI: 3.96-9.28,P:<0.05),based on C/C type,can increase the risk in CHD.As well,there are significant differences in the level of serum HCY between ACS group and stable angina group(P<0.05),and C/T type(OR:3.02,95%CI: 1.52-6.00,P:<0.05);T/T type(OR: 5.94,95%CI: 2.74-12.87,P:<0.05)and C/T+T/T type(OR: 3.74,95%CI: 1.94-7.22,P:<0.05),based on C/C type,can increase the risk in ACS group.There are significant differences in the mutation of MTHFR gene between CHD complicated with hypertension group and not complicated with hypertension group,however,there is no significant difference between CHD complicated with hyperlipidemia group and not complicated with hyperlipidemia group.There is no significant difference in the level of serum HCY between CHD complicated with hypertension group and not complicated with hypertension group,and the same of CHD complicated with hyperlipidemia group and not complicated with hyperlipidemia group.Conclusions There are significant differences in the level of serum HCY and the mutation ofMTHFR gene between CHD group and control group.The same result in the comparison of ACS group and stable angina group.There are significant differences in the mutation of MTHFR gene between CHD complicated with hypertension and not complicated with hypertension,however,there is no significant difference in the level of serum HCY between the two subgroups.There are no significant differences in the level of serum HCY and the mutation of MTHFR gene between CHD complicated with hyperlipidemia and not complicated with hyperlipidemia,indicating that both the mutation of MTHFR gene and the level of serum HCY unrelate with hyperlipidemia very well.