The Relationship Of Apolipoprotein E Gene Polymorphism To Metabolic Syndrome And Coronary Artery Disease

Ample epidemiological evidence confirms the clinical impression that cardiovascular risk factors: hypertension, diabetes,hyperlipidemia and obesity. The clustering of these disorders associated with the metabolic syndrome (MS) defined by the WHO in 1999. MS is influenced by the interaction of genetic and enviromental factors.Growing understanding of genetic factors playing an important role in the responsiveness of the disease in recent years.However,discoveries of genetic and enviromental nature of the MS should enhance our ability to intervene earlier and more effectively and therefore lesson the coronary heart disease (CHD) and should be a potential target for therapy.The aims of this study were to evaluate the features of the plasma lipid profile and the correlation with coronary heart disease(CHD) in the patients with metabolic syndrome(MS); and to assess the relationship of Apolipoprotein E ( ApoE ) gene polymorphism to MS and CHD.Methods: The patients with essential hypertension, diabetes mellitus or essential hypertension complicated with diabetes mellitus were divided into two groups, metabolic syndrome (WHO definition, MS+ n=96) and Non-metabolic syndrome (MS- n=107). ApoE genetype was determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The sequencing of the PCR product was determined by using fluorescent labeling automatic method to detect single nucleotidepolymorphisms (SNPs).Results:1 .There was a higher prevalence of CHD ( 58.6% vs 27.1 %, P=0.000 ) in MS+ complicated with that in MS-.2. Patients in MS were association with increased concentrations of TC ( 2.2 1.4 vs 1.7 0.9 mmo 1 /1, P= 0.006 ), While decreased concentrations of HDL-C( 1.1 0.3 vs 1.2 0.4 mmol/1, P= 0.011 ) .Logistic regression analysis showed that TC is a single risk factor of MS.3.The prevalences of the 2, 3, 4 allele were 0.064,0.815 and 0.121 respectively in the whole population.The frequency of the allele complied well with the Hardy-Weinberg equilibrium.4. There was an association between the frequency of e 4 allele and the MS or MS+CHD . The frequency of e 4 allele is higher in MS+ complicated with that in MS- ( 15.6% vs 8.9%, P=0.038) and so as to in MS+CHD (21.8% vs 7.3%, P=0.006 ) .on the contrary , the frequency of s 2 allele in the MS+CHD is lower than that in MS ( 0.9% vs 8.5%, P=0.009 ) .5.Patients carrying e 2 allele in MS were association with increased concentrations of TC ( 2.79 1.22 VS 1.78 1.01, P=0.021 ) complicated with those of 4.6. We determined the sequence of the ApoE gene using direct sequencing of the PCR products. ApoE gene analysis showed a nucleotide substitution of T to C at the sequence of the PCR products 137 and 210respectively in exon 4.These mutations were confirmed by the RFLP method.This study suggests that 4 allele tends to increase the risk of MS and CHD,and there was a strong association between the frequency of 4 allele and the MS+CHD.ApoE may be a candidat gene in MS.