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Effect Of MTHFR C677T Gene Polymorphism On Folic Acid Therapy In Stroke With Hyperhomocysteinemia

Posted on:2020-04-27Degree:MasterType:Thesis
Country:ChinaCandidate:Q Q ChenFull Text:PDF
GTID:2404330575499640Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
N5,N10-methylenetetrahydro-hydrofolate reductase(MTHFR)is a key enzyme in homocysteine(Hcy)and folate metabolism,epidemiological studies have confirmed that MTHFR gene polymorphism is susceptible to many diseases,the most important of which is stroke,and hyper homocysteinemia(HHcy)is one of the independent risk factors for stroke.Therefore,appropriate folic acid supplementation for stroke patients can reduce the level of Hcy in a certain extent,and it can preventing the diseases caused by its risk factors.Objective Systematically evaluateing the risk of susceptibility between stroke and MTHFR gene677 single nucleotide polymorphism(C667T),investigateing the multivariate relationship between MTHFR gene polymorphism and HHcy,and observeing the changes of Hcy levels in stroke patients with HHcy before and after folic acid treatment.Provideing evidence for better treatment of stroke with HHcy in clinic.Methods1.Base on the English database(Cochrane,Pubmed,Embase,Medline),Chinese database(Chinese Journal Full-text Database,Weipu Chinese Journal Database and Wanfang Digital Journal Full-text Database)to search for related literature on MTHFR C677 T gene polymorphism in stroke patients.The search period is from the time of construction to May 31,2018.According to the Cochrane systematic review method,the literature was extracted,the data was extracted,and the quality was evaluated.Meta-analysis was performed on the data using Rev Man 5.3 software.2.Between May 2017 and 2018,a total of 671 Han patients with MTHFR gene C677 T locus were enrolled in a department of encephalopathy and geriatrics in a top three hospital.The basic information such as age,gender,and laboratory indicators were recorded.CREA,BUN,etc.are entered into the Excel table for data analysis. 3.Patients with HHcy stroke were selected from 671 patients who were tested for MTHFR C677 T gene by case-control study.Patients with oral administration of 5 mg/d folic acid(once a day)were used as case group,and only conventional treatment was used without folic acid.The age,gender,diagnosis,basic treatment and case group were matched in the control group,a total of 84 cases.All patients were tested for Hcy concentration by collecting 2 ml of venous blood before admission,and the genotype was detected by MTHFR C677 T gene.After 3 weeks,the plasma Hcy values of the two groups were measured again,and recorded according to the three genotypes of MTHFR C677 T.Result1.Through literature research,the results of meta-analysis showed that the risk of TT genotype was higher than CC genotype [OR=2.17,95% CI(1.85-2.54),P?0.00001];the risk of TT genotype was also higher than that of TC+CC gene.Type [OR=1.90,95% CI(1.46-2.46),P<0.00001];the risk of TT+TC genotype was higher than CC genotype[OR=1.75,95%CI(1.44-2.12),P<0.00001];The differences were statistically significant.2.Through laboratory tests,671 cases of MTHFR C677 T gene distribution were 184 patients with CC type,299 patients with CT type,and 188 patients with TT type.The factors influencing HHcy were: MTHFR C677 T gene TT type [OR=3.401;95% CI,1.103-3.674,P=0.026],creatinine value was greater than normal range [OR=2.419;95% CI,1.023-4.370,P=0.044],urea nitrogen value is greater than the normal range[OR=1.931;95% CI,1.018-3.056,P=0.021],uric acid value is greater than the normal range [OR=1.811;95% CI,1.144-4.806,P=0.037],Age over 60 years old [OR=1.782;95%CI,1.162-2.973,P=0.019],gender male [OR=1.765;95%CI,1.323-2.749,P=0.028],smoker[OR=1.556;95%CI,0.632-9.317,P=0.037],drinker[OR=1.477;95%CI,0.761-8.012,P=0.041].3.The case-control study showed that the plasma Hcy level was significantly decreased in the case group after 3 weeks of treatment with 5mg/d folic acid.The TT type of patients in the three groups of patients had a maximum decrease of 31%,and the CC and CT patients decreased by approximately:24%,28%.In the control group,the concentration of Hcy decreased slightly after 3 weeks of routine treatment.Conclusion1.The key enzyme of Hcy metabolism,the MTHFR gene C677 T mutation,increases the risk of stroke.2.MTHFR gene TT type and BUN,CREA,UA value is greater than the normal range,gender is male,age is over 60 years old,smoking,drinking is the main risk factor for HHcy.3.For stroke patients with MTHFR gene HHcy,administration of 5 mg/d folic acid was effective in reducing Hcy levels,with TT patients being the most significant.
Keywords/Search Tags:MTHFR C677T, genetic polymorphism, homocysteine, hyper homocysteinemia, folic acid
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