A Preliminary Study Of The Relationship Between Promoter Methylation Of The ABCG1, GALNT2and HMGCR Genes And Coronary Heart Disease

Background and aims: DNA methylation is a stable and well understood epigeneticmarker. Increasing evidence indicates that many human diseases, including cancers andatherosclerosis, are either caused or influenced by abnormal DNA methylation. ABCG1,GALNT2and HMGCR are among the genes suggested by Genome-wide association study(GWAS) whose variants are associated with CHD and variations in plasma lipoproteins. Theaims of the present study are firstly to establish whether abnormal promoter region methylationof these three genes occurs in the cardiovascular system; secondly to explore the interaction ofthe methylation with the clinical characteristics in Han Chinese population; and thirdly toascertain whether the aforementioned methylation contributes to the risk of CHD.Methods and results: Methylation-specific polymerase chain reaction (MSP) technologywas used to examine the role of the aberrant gene promoter methylation in CHD in HanChinese population. A total of85CHD patients and54participants without CHD confirmed byangiography were recruited. The promoter methylation of the ABCG1gene washypermethylated in90.5%of the CHD subjects and29.6%of the non-CHD subjects. The CHDpatients showed a higher mean GALNT2gene promoter methylation index compared to thenon-CHD subjects (54.1%vs.27.8%).The promoter methylation of HMGCR gene was detectedin34.1%of the CHD subjects and22.2%of the non-CHD subjects. Our results indicated asignificant statistical association of promoter methylation of the ABCG1gene with increasedrisk of CHD (OR=22.859;95%CI,8.989-58.135; p<0.001and OR=19.966;95%CI,7.319-54.468; P*<0.001; P*: adjusted for age, gender, smoking, hypertension, and diabetes). Similarresults were obtained for that of the GALNT2gene (OR=3.067;95%CI,1.474-6.380; p=0.002and OR=2.978;95%CI,1.335-6.646; P*=0.008)(Table3), but not of HMGCR gene(OR=1.813;95%CI,0.829-3.965; P=0.134and OR=1.388;95%CI,0.572-3.371; P*=0.469).Moreover, we found the diabetes prevalence rate of the promoter methylation of the ABCG1gene was26.9%and6.5%in unmethylated subjects, CHD prevalence rate was82.8%and17.4%in unmethylated subjects. The GALNT2gene promoter methylation subjects’ mean age was62.10±8.21years old and57.28±9.87years in unmethylated subjects; methylationsubjects’s CHD prevalence rate was75.4%and50%in unmethylated subjects. The HMGCRgene promoter methylation subjects’ mean age was63.24±8.10years old and57.79±9.55years in unmethylated subjects. In addition, the smokers showed a lower mean HMGCR genepromoter methylation index compared to the non-smokers.Conclusions: The present work provides evidence to support the association of promoterDNA methylation status with the risk profile of CHD. Our data indicates that promoter DNAhypermethylation of the ABCG1and GALNT2genes, but not the HMGCR gene, is associatedwith an increased risk of CHD. CHD, age and smoking is likely to be an important factor ofDNA methylation.