Larouche_2026_J.Clin.Lipidol__

BACKGROUND: Persistent chylomicronemia (PC) is a rare condition characterized by plasma triglyceride concentration persistently >10 mmol/L despite treatment, reflecting a 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: To compare LPL DNAme in blood and adipose tissue of patients with PC or other causes of hypertriglyceridemia (HTG) and normotriglyceridemic controls. METHODS: DNA 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 at 22 cytosine-phosphate-guanine sites (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. RESULTS: No difference in LPL DNAme was observed in blood samples. In adipose tissues, patients with FCS were significantly less methylated at 2 CpGs located in the LPL gene body compared with other genotypes (delta = 2.85% and 3.78%, P = .011). When DNAme was analyzed according to HTG severity, the same CpGs were less methylated in patients with PC of any cause compared with other groups (delta = 4.55%, P = .002; delta = 7.70%, P < .001). CONCLUSION: In this study, the LPL DNAme signature in adipose tissue differed in patients with PC compared with others, highlighting that different factors might contribute to PC and its associated risks.