# Evaluating the Influence of CHI3L1 and PI3 Methylation in Allergic and Nonallergic Asthma

**Authors:** Selene Baos, Lucía Cremades-Jimeno, María Ángeles de Pedro, María López-Ramos, Rubén Fernández-Santamaría, Cristina Rosales-Ariza, Joaquín Quiralte, Fernando Florido, Nicolás González-Mangado, María Jesús Rodríguez-Nieto, Germán Peces-Barba, Joaquín Sastre, Blanca Cárdaba

PMC · DOI: 10.3390/biom15101363 · Biomolecules · 2025-09-25

## TL;DR

This study explores how DNA methylation of CHI3L1 and PI3 genes differs in allergic and nonallergic asthma patients compared to healthy individuals.

## Contribution

The study identifies DNA methylation patterns of CHI3L1 and PI3 genes in asthma subtypes and links them to potential biomarker roles.

## Key findings

- CHI3L1 and PI3 gene expression was significantly lower in asthmatic patients compared to healthy controls.
- CHI3L1 protein levels were higher in both allergic and nonallergic asthma patients.
- DNA methylation of CHI3L1 and PI3 was higher in asthmatic patients but not correlated with gene or protein expression.

## Abstract

Previously, we defined CHI3L1 and PI3 as genes related with asthma and severity by analysis of differential gene expression. In this study, we investigated the role of DNA methylation in their regulation, and their relationship with protein levels and clinical parameters. Peripheral blood mononuclear cells (PBMCs) and sera were collected from healthy controls (HCs), nonallergic asthmatic (NA), and allergic asthmatic (AA) patients. RNA and DNA were extracted from PBMCs using the trizol method. Gene expression was assessed by qRT-PCR, and DNA methylation of CpG sites near the promoters was analyzed using sodium bisulfite treatment followed by PCR amplification. DNA methylation analysis was performed using the Sequenom EpiTYPER platform. Protein levels were quantified by ELISA, and statistical analyses were carried out using GraphPad software. Consistent with previous findings, CHI3L1 and PI3 gene expression were significantly lower in asthmatic patients compared to controls. Conversely, CHI3L1 protein levels were higher in both patient groups, while PI3 protein showed no significant changes. DNA methylation analysis revealed higher overall DNA methylation percentages in NA and AA patients for both genes compared to HCs. Despite this, no significant correlations were observed between DNA methylation and gene or protein expression, although some correlations were observed with clinical parameters. In conclusion, CHI3L1 and PI3 represent potential asthma biomarkers, whose regulation may be partially influenced by DNA methylation, a mechanism more pronounced in asthmatic patients than in healthy subjects.

## Linked entities

- **Genes:** CHI3L1 (chitinase 3 like 1) [NCBI Gene 1116], PI3 (peptidase inhibitor 3) [NCBI Gene 5266]
- **Proteins:** CHI3L1 (chitinase 3 like 1)
- **Diseases:** asthma (MONDO:0004979), allergic asthma (MONDO:0004784), nonallergic asthma (MONDO:0004765)

## Full-text entities

- **Genes:** PI3 (peptidase inhibitor 3) [NCBI Gene 5266] {aka ESI, SKALP, WAP3, WFDC14, cementoin}, CHI3L1 (chitinase 3 like 1) [NCBI Gene 1116] {aka ASRT7, CGP-39, GP-39, GP39, HC-gp39, HCGP-3P}
- **Diseases:** Asthma (MESH:D001249), allergic asthmatic (MESH:D004342), asthmatic (MESH:D013224)
- **Chemicals:** trizol (MESH:C411644), sodium bisulfite (MESH:C009279)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12564470/full.md

## References

88 references — full list in the complete paper: https://tomesphere.com/paper/PMC12564470/full.md

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Source: https://tomesphere.com/paper/PMC12564470