Association Between DNA Methylation Of Lipid Metabolism-Related Genes With Dyslipidemia And Coronary Heart Disease

Objective: TBL2(transducin(β)-like 2),AMFR(Autocrine Motility Factor Receptor),HMGCR(HMG Co A Reductase),GRINA(Glutamate receptor,ionotropic,N-methyl-D-aspartate associated protein 1),FBXW7(F-box and WD-40 domain protein7),INSIFG1/2(Insulin-induced gene),SCAP(SREBP cleavage-activating protein),SREBF1/2(sterol regulatory element-bindingtranscription factors),MBTPS1(membrane-bound transcription factor protease site 1)genes are well-known genes involved in lipid metabolism.However,it is unclear whether the DNA methylation of these genes are related to dyslipidemia or coronary heart disease.In this study,we analyzed the DNA methylation levels of 11 genes,including TBL2,AMFR,and HMGCR,between the case group and the control group to explore the association between DNA methylation of lipid metabolism-related genes and dyslipidemia and coronary heart disease.Methods: A case-control study was used in this study.89 cases of dyslipidemia case group and 97 cases of control group were selected;35 cases of coronary heart disease group and 36 cases of control group were selected.Age and sex were matched between the two groups.Solexa sequencing was used to quantitatively analyze the gene promoter regions of 11 genes including TBL2,AMFR,and HMGCR to determine whether the methylation levels of the two groups of genes and the related Cp G sites were different.Specific DNA methylation haplotypes were also analyzed.Results: In the dyslipidemia case group and the control group,we found that the DNA methylation levels of TBL2 and GRINA genes are related to dyslipidemia.Logistic analysis revealed that methylation of TBL2 gene is a protective factor for dyslipidemia and DNA methylation of GRINA gene is a risk factor for dyslipidemia.At the same time,we found that the DNA methylation levels of 52 Cp G locis in 11 genes were related to dyslipidemia;a total of 38 DNA methylation haplotypes were statistically different in the two groups.In the coronary heart disease case group and the control group,the DNA methylation level of GRINA gene was related to coronary heart disease.Logistic analysis revealed that GRINA gene DNA methylation is not the factor of coronary heart disease.At the same time,we found that the DNA methylation levels of a total of 26 Cp G sites of 11 genes were related to coronary heart disease;and a total of 30 DNA methylation haplotypes were statistically different in the two groups.Conclusion: In Xinjiang Han population,DNA methylation of TBL2 and GRINA genes are related to the occurrence of dyslipidemia,and Cp G sites of multiple lipid metabolism-related genes are related to dyslipidemia and coronary heart disease.