The Relationship Of Methylenetetrahydofolate Reductase Gene C677T Polymorphism And Plasma Homocysteine Level With Premature Coronary Artery Disease

BackgroundPremature coronary heart disease(PCHD) refers to the time of breaking outcoronary heart disease(CHD) for male <55years old，female <65years old，which is aspecial form of CHD．PCHD is a multifactorial disease, in which genetic factors play animportant role in pathogenesis of PCHD. Therefore, researching genetic risk factors ofPCAD is a very important practice for prevention and treatment of the PCAD.Growingevidence indicate that high plasma homocysteine(Hcy) level is closely associated withthe risk of CHD and that high Hcy level constitute a major independent factor for CAD.Not only modified by environmental factors, but plasma Hcy concentration were highlyheritable.One of the most key enzymes which regularize Hcy metabolism is themethylenetetrahydofolate reductase (MTHFR),and its genetics is coded by MTHFRgene. The heritability of Hcy may be associated with genetic polymorphisms in theMTHFR C677T.So far,several studies in selected populations have reported the associationbetween common C677T variant of the MTHFR with the risk of PCHD, but whetherthis variant in different reports are associated with the risk of PCHD is unclear. Thedisaccord may be related to lots of factors such as the difference ofrace,nationality,region and latitude,polugenic,inheritance,statistical,methods,sample size There were no reports about the relationship of MTHFR C677T polymorphism withpremature coronary heart disease in Han patients in the Suwan region in China. In thisdissertation, a case-control study has been carried out to assess the associations of theMTHFR C677T polymorphism and plasma Hcy level with the risk of PCHD in Suwanpopulation.Objective1.The study was designed to investigate the polymorphism of C677T of MTHFRin Suwan PCHD patients, compared with healthy control; to compare and analyze thedifference of the distribution of genotypes and alleles between case group and controlgroup.2. To analyze the association of the polymorphism of C677T of MTHFR with theHcy levels of PCHD patients in Suwan Han people.MethodsTo adopt case-control study method in this study.1.100patients with PCHD and103healthy controls from the Suwan region Hanpopulation in China were interviewed. The genomic DNA was extracted from the whiteblood cells in peripheral blood.General data of these people were collected and wereanalyzed by descriptive statistics.2. The levels of plasma Hcy were measured using enzymatic cycling assay.3. To use the way of polymerase chain reaction(PCR)and the restriction fragmentslength polymorphism(RFLP) analyse the C677T polymorphism of MTHFR gene. 4.The genotype frequencies of polymorphism were calculated for Harder-Weinbergequilibrium,whether these data could correspond the group representative of this areawould be estimated.5. The genotype frequencies and allele frequencies of polymorphism werecalculated respectively in both case group and control group. Meanwhile, to compare databetween case group and control group.6.To compare the average levels of plasma Hcy according to different classification.Results1.The average level of Hcy in the case group was higher than that in the controlgroup (P＜0.05)2.The genotype distribution in C677T of MTHFR gene reached Harder-Weinbergequilibrium in both case group and control group(P＞0.05),indicated that thepopulation in present study were selected randomly.3. Comparison of the control group,the frequencies of genotype TT and allele T ofC677T of MTHFR gene in case group were significantly higher.(P＜0.05).4.There was significant difference of the average levels of Hcy among the differentgenotypes(P＜0.05).5.Comparison of homozygote CC, homozygote TT and heterozygote CT+homozygote TT increase susceptibility of PCHD(P＜0.05).6. The average levels of Hcy of CC and CT genotypes in case group was higherthan those of the same genotypes in control group(all P＜0.05)；the average level ofHcy of TT genotype in case group was not difference with that of the same genotype incontrol group(P＞0.05). Conclusion1. The MTHFR gene C677T polymorphisms might be associated with PCHD.Thepatients with TT genotype might have more susceptibility of PCHD than others with CCgenotype.The individuals with T allele might have more risk of PCHD.2. The MTHFR677C→T mutation might enhance the level of plasma Hcy.3.There might enhance the risk of PCHD,when the level of plasma Hcy hadincreased.