Genetic analysis of DNA methylation in dyslipidemia: a case-control study

Coronary heart disease has become the leading cause of death in developed countries, and dyslipidemia is closely associated with the risk of cardiovascular disease. Dyslipidemia is caused by the abnormal regulation of several genes and signaling pathways, and dyslipidemia is influenced mainly by genetic variation. AMFR, FBXW7, INSIG1, INSIG2, and MBTPS1 genes are associated with lipid metabolism. In a recent GWAS study, the GRINA gene has been reported to be associated with dyslipidemia, but its molecular mechanism has not been thoroughly investigated. The correlation between the DNA methylation of these genes and lipid metabolism has not been studied. This study aimed to examine the relationship between the DNA methylation of these genes and the risk of dyslipidemia by comparing the methylation levels of dyslipidemia and control samples.

A case-control research method was used in this study. The patient's blood samples were collected at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University. In the Xinjiang Han population, 100 cases of hyperlipidemia and 80 cases of the control group were selected. The two groups were age and gender-matched. Quantitative methylation analysis of CpG sites in the gene promoter regions of six genes was performed by Solexa high-throughput sequencing.

The DNA methylation levels of 23 CpG sites in six genes were shown to be associated with hyperlipidemia, and a total of 20 DNA methylation haplotypes showed statistically significant differences between the two groups. When compared with the control group, the dyslipidemia group had significantly higher levels of methylation in the GRINA gene (2.68 vs 2.36, P = 0.04). Additionally, we also discovered a significant methylation haplotype of GRINA (P = 0.017).

The findings of this study reveal that the DNA methylation of GRINA increases the risk for dyslipidemia in humans.