👤 Catherine Laprise

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. To compare LPL DNAme in blood and adipose tissue of patients with PC or other causes of hypertriglyceridemia (HTG) and normotriglyceridemic controls. 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. 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 (Δϐ = 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 (Δϐ = 4.55%, P = .002; Δϐ = 7.70%, P < .001). 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. Show less

Food allergy (FA) is a great public health concern with an increased prevalence in the last decades. The underlying development mechanisms of FA and food sensitization (FS), which represents the first stage of development of FA, are influenced by environmental, epigenetic, and genetic factors. DNA methylation is an important epigenetic mediator of gene-environment interactions and key to understanding these mechanisms. Studies have linked whole-genome DNA methylation profile to FA and FS, but they all use methylation arrays. Methylation sequencing captures target regions of methylome with an extensive coverage. Thus, our objective was to identify CpG sites in genome-wide immune regulatory regions associated with FS and test their association with genetic variants using methylation quantitative trait loci (mQTL) analysis in French-Canadian individuals. In 114 individuals from the Saguenay-Lac-Saint-Jean asthma family cohort, a total of 10 CpG sites out of 5,233,004 CpG sites were associated with the FS status (P < 1 × 10 To our knowledge, this is a unique association study between FS and DNA methylation using targeted bisulfite sequencing across the genome. This approach provides high-resolution assessment of genome-wide functional methylome that yields valuable understandings to this field of research. The results reveal potential relationships between FS, CpG sites, and genetic variants located in genes involved in allergic diseases. This provides potential insights on the underlying effects of DNA methylation and genetic variants on FS and possibly the pathogenesis of FA. Further epigenome-wide studies on larger samples combined with genome-wide genotyping are needed to validate the results and verify the biological potential of these CpG sites. Show less

The epigenetic mechanisms of asthma remain largely understudied in African Americans and Hispanics/Latinos, two populations disproportionately affected by asthma. We aimed to identify markers, regions and processes with differential patterns of DNA methylation (DNAm) in whole blood by asthma status in ethnically diverse children and youth, and to assess their functional consequences. DNAm levels were profiled with the Infinium MethylationEPIC or HumanMethylation450 BeadChip arrays among 1226 African Americans or Hispanics/Latinos and assessed for differential methylation per asthma status at the CpG and region (differentially methylated region (DMR)) level. Novel associations were validated in blood and/or nasal epithelium from ethnically diverse children and youth. The functional and biological implications of the markers identified were investigated by combining epigenomics with transcriptomics from study participants. 128 CpGs and 196 DMRs were differentially methylated after multiple testing corrections, including 92.3% and 92.8% novel associations, respectively. 41 CpGs were replicated in other Hispanics/Latinos, prioritising cg17647904 ( We report novel whole-blood DNAm markers for asthma underlying key processes of the disease pathophysiology and confirm the transferability of previous asthma DNAm associations to ethnically diverse populations. Show less