Association Of ApoE Gene Polymorphism With The Risk Of Atrial Fibrillation In Han People Of Shandong Province

BACKGROUNDAtrial fibrillation(AF)is the most common cardiac arrhythmia in clinical practice.With high morbidity and mortality,AF is increasingly become a serious threat to hunman health.However,the pathological mechanisms behind it is not very clear and the treatment effect is limited.So it is vital important to study and reveal the reasons and mechanisms in order to offer a good idea and therapy methods to AF.Apolipoprotein E(ApoE)is one of the major apolipoproteins in plasma,which is discovered in very low density protein in normal person.ApoE is a polymorphic protein,and the common genetic alleles including ?2,?3,?4.Among them,s3 is the most common isomer indentified as a wild type,and ?2 and s4 are called as the variants.Participated in the process of transformation and metabolism of lipoproteins and the balance of cholesterol,ApoE plays an important role in the regulation of lipids'level.ApoE is closely related with the risk of disorder of lipid metabolism,coronary heart disease,atherosclerosis,Alzheimer's disease and stroke.There is almost no research on the relationship between ApoE and AF at home or abroad.However,it can be inferred that ApoE is involved in the development of AF according to the pathogenesis of AF and the function and role of ApoE.It is recognized that the occurrence and persistence of AF is closely related to the process of oxidative stress and inflammation.At the same time,it is believed that ApoE is associated with oxidative stress and inflammation.With a strong proinflammatory effects,the ApoE ?4 allele can activate NF-?B and release high level of TNF-?,IL-1?,MIPl-a and other pro-inflammatory molecules and low level anti-inflammatory molecules,including IL-10.Therefore,it can be deduced that ApoE ?4 allele may participate in the process of AF.The current researches have been reported that the occurrence of AF is related with the level of plasma lipids,picardial fat thickness,pericardial fat,the thoracic and abdominal visceral fat and body weight.As an important apolipoprotein involved in lipid metabolism,ApoE affects the level of blood lipids,body fat and weight,which further supports the hypothesis that the polymorphism of ApoE gene may be involved in the prevalence and persistence of AF.ApoE may also increase the incidence of AF by affecting the level of blood lipid and promoting the occurrence of cardiovascular diseases.The purpose of this study was to investigate the correlation between ApoE gene polymorphism and the prevalence of AF in Han people of Shandong province.OBJECTIVEExplore the correlation of the polymorphism of 112 locus and 158 locus in ApoE gene with the prevalence of AF in Han people of Shandong province.Explain the correlation of ApoE's genotype and phenotype with AF.METHODS92 patients diagnosed with AF were included in the group of AF,and 93 patients in the same period diagnosed without AF were included in the control group.Clinical general information of all patients were collected,especially white blood cells(WBC),neutrophils percent,C reactive protein(CRP),triglyceride(TG),total cholesterol(TC),low density lipoprotein(LDL),high density lipoprotein(HDL).Whole blood was colleced and then the genomic DNA was extracted.Microarray was adopted to detect the polymorphism of 112 locus and 158 locus in ApoE gene.Statistical analysis:the count datum were compared by chi square test and the Fisher exact test is used when the count is less than 5.The measurement datum were compared with t test.The multi-factor analysis of the AF related factors using binary Logistic regression analysis.P>0.05 was considered as statistically significant.RESULTS1.Compared with the control group,the level of triglycerides and high density lipoprotein cholesterol was reduced in the AF group.On the contrary,the low-density lipoprotein cholesterol level was elevated in the AF group and the difference was statistically significant(P<0.05).No significant difference was found between the two groups in the total cholesterol(P>0.05).2.No significant difference was found between the two groups in the count of white blood cell and the percent of neutrophile granulocyte(P>0.05).Compared with the control group,the level of CRP was significantly increased and the difference was statistically significant(P<0.05).3.Both the AF group and control group were in accordance with the Hardy-Weinberg's law of genetic equilibrium.Compared with the two groups,there was significant difference in genotype frequency and allele frequency of ApoE gene at 112 locus(P<0.05),While there was no difference in genotype frequency and allele frequency at the 158 locus(P>0.05).There was statistically different in ApoE phenotype(P<0.05)and the incidence of AF was higher in the type of ApoE4.4.HDL,CRP and ApoE4 are all independently associated with the occurrence of AF[HDL(OR=0.357,95%CI:0.132-0.965,P=0.042),CRP(OR=1.288,95%CI:1.051-1.579,P=0.015),ApoE4(OR=2.224,95%CI:1.018-4.861,P=0.045)].HDL is the protective factor while ApoE4 and CRP are risk factors for AF.LDL has no correlation with AF(OR=1.620,95%CI:0.916-2.864,P=0.097),and it can not be exclude that age is a risk factor for AF(OR=1.025,95%CI:1.000-1.051,P=0.049).CONCLUSIONSThere is a certain correlation between the ApoE gene polymorphism and the occurrence of AF in the Han population of Shandong province.ApoE4 is a sensitive phenotype of atrial fibrillation,and the incidence of AF is higher in the patients with the type of ApoE4.