The Association Of ACE2 Gene A9570G Variation With Type 2 Diaiabetes Mellitus With Coronary Heart Disease And The Severity Of Coronary Lesions In Han Nationality In Guangdong Province

BackgroundBecause the change of the people living standard,working pattern,food and drink construction,as well as the average duration of life extend,the outbreak rate of diabetes mellitus(DM) increases high year by year.DM is jeopardizing to the human body next to cancer and Cardio-cerebral vascular disease as non- communicable disease.In fact,DM is not fear,but terrible of it is complications.The harm which DM brings is almost come from its complications.The most serious complications is cardiovascular disease,which is a main reason to die for DM Patients.The epidemiology and clinical research has confirmed that DM patients are more susceptible to coronary heart disease(CHD),but the coronary artery pathological changes of DM patients with CHD often is extensive and serious,which leading to difficult and costly treatment.So,definiting its etiopathogenisis and seting up the early diagnosis method is good for clinic.Actually,the artherosclerosis is a result of the interaction of various risk factors.DM patients which frequently accompanied cardiovascular risk factors such as lipid metabolism disorder,high blood pressure and so on.But some study considered the morbidity of CHD in DM patients and the severity of vascular lesion had a significant difference even if the control of blood glucose and the risk factors of CHD are similar,in addition,the morbidity of CHD in DM Patients is different in different nationality.This shows that the traditional cardiovascular risk factors can not fully explain the different incidence of CHD in DM patients and the different performance of coronary artery pathological changes, which may be associated with individual genetic background.At present most people considered T2DM as a kind of multifactorial disorder caused by the interaction of various risk factors such as heredity,environment, behavior and other risk factors.The result of genetics etiopathogenisis research indicated that T2DM is a kind of polygene hereditary diseases and may be its complications are subjected to the patient's heredity background influence,too.As T2DM is highly heterogeneity,therefore,it is not easy to confirm which are the predisposing genes of T2DM and its complications.Some research considered the gene related to lipid metabolism,lipoprotein oxidation and blood clotting maybe the main candidate gene.Recently,with the deep investigate of RAS system,it was confirmed by plenty of experiments that the RAS system play role in the development of DM and its complications,so the polymorphism of the related genes in members of RAS was interesting,but the research result was imcompatible.It is necessary to investigate deeply.ACE2 was a new member of RAS,which is antagonistic to ACE, also played an important role in RAS.At present there is research indicated that the polymorphism of some sites in the gene is related to development or phenotype of some disease.In this study,PCR-RFLP analysis was adopted to detect the polymorphism of the ACE2 gene A9570G in Han nationality in Guangdong province. Through analysis of the disposition of the polymorphism of the ACE2 gene A9570G, preliminary revealed to the correlation between A9570G polymorphism in ACE2 gene and T2DM complicating with CHD in Han nationality in Guangdong province. The results maybe contribute to investigate the genetic mechanism of T2DM complicating with CHD on molecule level,look for and establish effectively onset risk and preonset diagnosis technique for cardiovascular diagnose,find and determine which genotype had impact on the severity of coronary artery lesions,which will have importance practical value.Objective1 To investigate the correlation between A9570G polymorphism in ACE2 gene and T2DM complicating with CHD in Han nationality in Guangdong province, preliminary identification of the relevant disease susceptibility gene.2 Screening of sensitive genetype for type 2 diabetes mellitus complicating with coronary heart disease,contributing to the early prevention and treatment of the susceptible population.3 Find and determine which genetype had impact on the severity of coronary artery lesions.Formulating therapeutic regimen based on the genetype to make the treatment individualization and utility.4 From the perspective of genetics to find the risk factors of T2DM with CHD is contributed to reveal the genetic etiology and pathogenesis.Methods1 Subjects:The study groups include 100 control subjects,208 T2DM patients complicating with or without CHD,90 patients merely with CHD.All subjects on an empty stomach were taken suction 4ml peripheral venous blood,cryopreservation, pre-emergency.2 Methods:A9570G polymorphism of ACE2 gene were studied by PCR-RFLP analysis and the general clinical data and the biochemical indicators all were recorded in this study, then analyzing the correlation between A9570G polymorphism in ACE2 gene and T2DM complicating with CHD.Logistic regression analysis is used to find the independent risk factor.T2DM group and T2DM complicating with CHD group were divided into groups by different genetypes respectively,and then analyzing the correlation between genetype and the severity of coronary artery lesions,evaluated by the Genisini score and the number of major coronary arteries with more than 75% luminal obstructions.Results1 The A9570G polymorphism of ACE2 gene was detected in Han nationality in Guangdong province.In male the A/G allele frequency is 0.56/0.44,in female the A/G allele frequency is 0.52/0.48,the AA/AG/GG genotype distribution is 0.24/0.56/0.20,which is consistent with Hardy-weinberg balance.Compared with HongKong people,genotype distribution and allele frequencies of A9570G were similar,and compared with Caucasian,there had a significant difference.2 In female,there had not a significant different among four groups in allele frequencies and genotype distribution of A9570G(X~2=0.032,P=0.999 and X~2=0.752, P=0.993).In male,there had a significant different among four groups in genotype distribution and allele frequencies of A9570G(X~2=11.972,P=0.007).Multiple comparison between four groups show that compared with control group,T2DM group,CHD group,the G allele in T2DM+CHD group is significantly high and there are no difference between control group,T2DM group and CHD group.3 Analyzed with non-conditional multivariate Logistic regression analysis,the result showed in male the G allele is a independent risk factor for patients with T2DM to suffering CHD(Exp(B)=2.301,95%CI 1.041-5.084),but G allele is not a independent risk factor in female(Exp(B)=0.561,95%CI为0.88-3.587). 4 In male,the Genisini coronary score and the number of major coronary arteries with more than 75%luminal obstructions in patients with G genotype in T2DM with CHD group were significantly higher than those in patients with A genotype(X~2=6.297,P=0.012 and Z=-2.823,P=0.005).This difference were not detected in female(X~2= 0.020,P=0.990 and X~2=0.791,P=0.673).Not only in male, but in female,the Genisini coronary score and the number of major coronary arteries with more than 75%luminal obstructions were similar in patients with different genotype in T2DM group(in male,X~2=2.035,P=0.154 and Z=-0.778,P=0.436.in female,X~2=0.021,P=0.989 and X~2=1.854,P=0.396).ConclusionOur data indicate that the distribution of polymorphism of ACE2 gene had an ethnic difference.The polymorphism of A9570G in the ACE2 gene is associated with T2DM complicating CHD and G allele maybe a predisposing genes and a independent risk factor for male to suffering T2DM complicating CHD.The polymorphism of A9570G in the ACE2 gene maybe not associated with T2DM and CHD in patients without T2DM.In male,G genetype is associated with the severity of coronary artery lesions in patients with T2DM complicating CHD.Our data also indicate that T2DM complicating CHD is the result of the interaction of various risk factors.