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Correlation Between Methylenetetrahydrofolate Reductase Gene C677T Polymorphism And Coronary Heart Disease In Han Population Of Kunming

Posted on:2020-09-02Degree:MasterType:Thesis
Country:ChinaCandidate:G F YangFull Text:PDF
GTID:2404330602454581Subject:Internal Medicine
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Objective:As one of the key enzymes in folate metabolism,methylenetetrahydrofolate reductase(MTHFR)plays an important role in biochemical processes such as DNA methylation and synthesis.The M677R gene C677T mutation can make the enzyme unstable to heat,resulting in decreased enzyme activity,causing elevated levels of serum homocysteine(HCY),thereby promoting cardiovascular disease.The purpose of this study is to analyze the distribution of MTHFR C677T gene polymorphism in Han population in Kunming,and its relationship with HCY and blood lipid levels,and to explore the relationship between it and the degree of coronary artery disease.provide a reference for early screening of coronary lesions and predicting the extent of the disease.Methods:All the patients were Han nationality.From March 2017 to March 2019,as the Experimental group,they went to the Second Affiliated Hospital of Kunming Medical University for coronary heart disease patients,including 99 males and 50 females.The control group was the general health checkup of the Second Affiliated Hospital of Kunming Medical University,including 20 males and 40 females.All subjects were asked to complete a questionnaire including gender,age,occupational status,smoking history,drinking history,past special medical history and family history.To further investigate the association between serological markers and the number of vessels involved in coronary artery disease,according to the medical history and number of lesions on the basis of coronary angiographic,the following three subgroups were included:69 patients with coronary artery disease with single vessel disease and 46 patients with double-vessel disease,34 patients with three-vessel disease.Collect general information such as blood glucose,blood lipids,blood pressure,height,weight,body mass index,the history of diabetes or smoking.and other traditional risk factors for coronary heart disease,as well as biochemical indicators such as liver and kidney function,myocardial enzymes,and plasma HCY levels.After the blood samples were collected on an empty stomach to extract the genomic DNA of interest,The polymorphism of MTHFR C677T was analyzed by Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Results:1.Distribution of MTHFR C677T genotype in Han population of KunmingWe observed three genotypes,CC,CT and TT.The CC,CT,and TT gene carriers in the Control group were 31,25,and 4,respectively,accounting for 51.6%,41.67%,and 6.67%,The CC,CT,and TT gene carriers in the Experimental group were 45,65 and 39,and the proportion was 30.20%,43.62%,and 26.17%.The hardy-Weinberg genetic balance test was performed separately,and the difference was not statistically significant(P>0.05).2.Analysis of risk factors for coronary heart diseaseAge,gender,hypertension,smoking,Lp(A),LDL-C,and HCY levels were significantly different between the CHD group and the control group(p<0.05).Coronary heart disease was older,smoking,It is more common in men with high blood pressure and high Lp(A)and LDL-C levels.Multiple comparisons suggested that HCY levels were different between the non-lesion group and each subgroup.One group and two groups,one group and three groups had intra-group differences,and the difference was statistically significant(p<0.05).3.MTHFR C677T gene polymorphism and HCY,blood lipid correlationHCY levels were different among different MTHFR C677T genotypes,and HCY levels were highest in TT genotypes,followed by CT genotype carriers,and the difference was statistically significant(p<0.05).Multivariate unconditional logistic regression showed that the probability of HHC Y in TT genotype carriers was 11.676(3.402-40.076)times that of CC genotype carriers;the possibility of CT genotype carriers HHCY was CC type 3.099(1.334)-7.201)times.Secondly,the probability of HHCY in men is 4.002(1.425-11.245)times that of women with HHCY;the probability of developing HHCY for every 1 year of age is 1.067(1.034-1.101)times.The MTHFR C677T gene polymorphism and blood lipid levels showed that the CT and TT genotypes were higher than the CC genotype TC,especially in the TT genotype;the LDL-C levels also had similar characteristics for Lp(A).The TT genotype had higher Lp(A)levels than the CC genotype,and the TT genotype had higher Lp(A)levels than the CT genotype.There was no sig1ificant difference between CT genotype and CC genotype.Correlation between blood Hey levels and blood lipid levels showed that HCY levels were negatively correlated with TG,positively correlated with LDL-C,Lp(A)(p<0.05),correlation intensity r<0.7;and cholesterol(TC),high density There was no significant correlation between lipoprotein(HDL-C).4.Analysis of factors related to the degree of coronary vascular diseaseThe pearson chi-square test showed that the proportions of CC,CT and TT genotypes were 51.76%,41.67%and 6.67%,respectively,and 37.68%,50.72%and 11.59%in the 1 group.28.26%,41.3%,30.43%in the 2 groups;17.65%,32.35%,50%in the 3 groups.Further multivariate ordered logistic regression showed that under the premise of correcting the influence of other factors,the possibility of increased number of lesions in patients with genotype TT was 5.775(2.492-13.382)times that of patients with genotype CC;the number of lesions in patients with genotype CT increased.The probability is 1.519(0.803-2.871)times that of patients with genotype CC;the probability of an increase in the number of hypertensive lesions is 2.047(1.068-3.922)times;the probability of an increase in the number of lesions per 1 year of age is The original 1.049(1.027-1.072)times;the probability of an increase in the number of lesions per unit of Lp(A)is 1.029(1.013-1.044)times;the possibility of an increase in the number of lesions per unit of HCY is increased.It is the original 1.04(1.02-1.061)times.Conclusion:1.The distribution of MTHFR C677T gene in Han nationality in Kunming is polymorphic and representative in the population.2.High levels of age,hypertension,smoking,Lp(A),LDL-C,and HCY may be risk factors for coronary heart disease.3.The MTHFR C677T genotype polymorphism is associated with HCY and lipid levels.Among them,the TT gene homozygous mutant carriers had significantly higher levels of HCY,TC,LDL-C,and Lp(A).4.MTHFR C677T genotype,hypertension,age,Lp(A),HCY levels may be independent risk factors for the increase of coronary vascular lesions.MTHFR C677T genotype may lead to the development of coronary heart disease by affecting HCY and blood lipid levels.
Keywords/Search Tags:Han nationality, Kunming area, methylenetetrahydrofolate reductase, gene polymorphism, homocysteine
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