Lipoprotein lipase DNA methylation in the adipose tissue of patients with persistent chylomicronemia

BackgroundPersistent chylomicronemia (PC) is a rare condition characterized by plasma triglycerides concentration sustainably >10 mmol/L despite treatment, reflecting lack of lipoprotein lipase (LPL) bioavailability.PC encompasses patients with the familial chylomicronemia syndrome (FCS) and patients with multifactorial PC.Life habits and environmental factors are known modulators of DNA methylation (DNAme) which can influence access to the LPL gene and possibly contribute to the expression of PC. Objective J o u r n a l P r e -p r o o fTo compare LPL DNAme in blood and adipose tissue of patients with PC or other causes of hypertriglyceridemia (HTG) and normotriglyceridemic controls. MethodsDNA was extracted from blood and adipose tissue in 186 participants: 31 with PC (21 FCS, 10 multifactorial PC), 125 with HTG and 30 controls.DNAme was measured using pyrosequencing in 22 CpGs located in the promoter and between the first exons of the LPL gene.Differences in LPL DNAme were assessed according to the genotype and severity of HTG. ResultsNo difference in LPL DNAme was observed in blood samples.In adipose tissues, patients with FCS were significantly less methylated in two CpGs located in the LPL gene body compared to other genotypes (=2.85% and 3.78%, p=0.011).When DNAme was analyzed according to HTG severity, the same CpGs were less methylated in patients with PC of any cause compared to other groups (=4.55%,p=0.002 and =7.70%, p<0.001). ConclusionIn this study, LPL DNAme signature in the adipose tissue differed in patients with PC compared to others, highlighting that different factors might contribute to PC and associated risks.