What is the clinical evidence from this study?

Study design: Observational. Population: Persistent chylomicronemia and hypertriglyceridemia (n=186). Primary outcome: DNA methylation percentage at CpG sites 18 and 19 in subcutaneous adipose tissue of the LPL gene (Δβ = 4.55% (CpG18), P = .002; Δβ = 7.70% (CpG19), P < .001 comparing PC vs other groups; Δβ = 5.13% (CpG18), P = .006 and Δβ = 7.93% (CpG19), P < .001 comparing PC of any cause vs controls, p=≤ .002 for CpG18 and < .001 for CpG19).

March 3, 2026Open Access

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

Q: What are the key findings of this study?

Patients with persistent chylomicronemia had significantly lower DNA methylation at CpG18 and CpG19 in adipose tissue LPL gene by up to 7.70% compared to hypertriglyceridemic and normotriglyceremic controls.

Key Result

Patients with persistent chylomicronemia had significantly lower DNA methylation at CpG18 and CpG19 in adipose tissue LPL gene by up to 7.70% compared to hypertriglyceridemic and normotriglyceremic controls.

Key Points

Lipoprotein lipase DNA methylation is altered in patients, indicating potential biomarker utility.
Key evidence shows significant differences in DNA methylation levels compared to controls, with implications for metabolism.
Observational analysis across affected individuals reveals specific methylation patterns in adipose tissue.
Findings highlight the need for further investigation into the role of DNA methylation in lipid disorders.

Study Design

Type

Observational (n=186)

Multicenter

Structured PICO

Does LPL DNA methylation in blood and adipose tissue differ between patients with persistent chylomicronemia, other hypertriglyceridemia, and normotriglyceridemic controls?

Population

186 participants: 31 with persistent chylomicronemia (21 familial chylomicronemia syndrome, 10 multifactorial), 125 with hypertriglyceridemia (HTG), and 30 normotriglyceridemic controls.

Comparator

Normotriglyceridemic controls and patients with other causes of hypertriglyceridemia

Outcome

Lipoprotein lipase (LPL) DNA methylation in blood and adipose tissuesurrogate

Patients with persistent chylomicronemia exhibit a distinct lipoprotein lipase DNA methylation signature in adipose tissue, suggesting epigenetic factors may contribute to the condition.

Main Result

Effect estimate: Δβ = 4.55% (CpG18), P = .002; Δβ = 7.70% (CpG19), P < .001 comparing PC vs other groups; Δβ = 5.13% (CpG18), P = .006 and Δβ = 7.93% (CpG19), P < .001 comparing PC of any cause vs controls

p-value: p=≤ .002 for CpG18 and < .001 for CpG19

Limitations

Study conducted in a genetic founder population in Saguenay-Lac-Saint-Jean, Canada limiting generalizability.
Sample size relatively small given rarity of persistent chylomicronemia and familial chylomicronemia syndrome.
Gene expression profiling to correlate DNA methylation was not performed but is underway.
Data limited to DNA methylation; other epigenetic marks were not assessed.

Abstract

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.

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