ABCA1, ADIPOQ, APOE, FSTL4, and KCNQ1 Gene DNA Methylation Correlates with Lipid Profiles in Mexican Populations

<b>Background</b>: Dyslipidemia, a significant modifiable risk factor for cardiovascular disease (CVD), represents a major global health challenge, particularly influenced by complex genetic and environmental interactions, mainly in indigenous populations. <b>Methods:</b> In this study, DNA samples from 80 individuals belonging to various indigenous ethnic groups from northern and southern Mexico were analyzed to evaluate DNA methylation profiles and its correlation to lipid levels and other clinical parameters. Ten genes associated with metabolic changes were investigated using targeted bisulfite sequencing. <b>Results:</b> Our results revealed significant correlations between methylation in genes such as <i>ABCA1</i>, <i>ADIPOQ</i>, <i>APOE</i>, <i>FSTL4</i>, and <i>KCNQ1</i> and clinical parameters including body mass index (BMI), lipid profiles, and body fat. Of the 151 CpG sites analyzed, 16 showed statistically significant correlations. Specifically, two <i>ABCA1</i> CpGs sites correlated with BMI (<i>p</i> = 0.015) and triglycerides (<i>p</i> = 0.03); three <i>ADIPOQ</i> sites correlated with low-density lipoprotein cholesterol (LDLc) (<i>p</i> = 0.03, <i>p</i> = 0.005, <i>p</i> = 0.04, respectively); one <i>APOE</i> site correlated with BMI (<i>p</i> = 0.04), another with total cholesterol (<i>p</i> = 0.004) and triglycerides (<i>p</i> = 0.03) and two more with high-density lipoprotein cholesterol (HDLc) (<i>p</i> = 0.02 and <i>p</i> = 0.005, respectively); one <i>FSTL4</i> CpG site with body fat (<i>p</i> = 0.02), another with total cholesterol (<i>p</i> = 0.02), one more with HDLc (<i>p</i> = 0.01), and another one with triglycerides (<i>p</i> = 0.01); and two <i>KCNQ1</i> CpG sites correlated with body fat (<i>p</i> = 0.01 and <i>p</i> = 0.04, respectively). <b>Conclusions</b>: These findings show potential novel biomarkers for dyslipidemia risk. This research highlights the importance of understanding methylation changes in indigenous populations for developing personalized interventions and prevention strategies that could improve healthcare by linking epigenetic factors to CVD risk.