- 【Updated on May 12, 2025】 Integration of CiNii Dissertations and CiNii Books into CiNii Research
- Trial version of CiNii Research Knowledge Graph Search feature is available on CiNii Labs
- 【Updated on June 30, 2025】Suspension and deletion of data provided by Nikkei BP
- Regarding the recording of “Research Data” and “Evidence Data”
A cis-eQTL allele regulating reduced expression of CHI3L1 is associated with late-onset adult asthma in Japanese cohorts
Search this article
Description
The chitinase-like protein YKL-40 plays a major role in inhibiting the inflammasome. Deregulation of inflammasome activation is emerging as a key modulator of pathologic airway inflammation in patients with asthma. We determined whether cis-expression quantitative trait loci (eQTLs) of the gene that encodes YKL-40, chitinase 3-like 1 (CHI3L1), are involved in the onset of asthma or in specific asthma phenotypes.This case-control study, which was conducted at the University of Tsukuba, Japan, included a total of 2709 adults from the Tsukuba genome-wide association study (GWAS) cohort (734 healthy volunteers and 237 asthma patients), the Tsukuba replication cohort (375 healthy adult volunteers and 381 adult asthma patients), and the Hokkaido replication cohort (554 healthy adult volunteers and 428 adult asthma patients). Among 34 cis-eQTLs in CHI3L1 in the lung, rs946261 was associated with adult asthma in these Japanese cohorts. The genetic impact of rs946261 on asthma was also examined according to the age at onset and adult asthma clusters.In the Tsukuba GWAS cohort, the C allele at rs946261 was significantly associated with reduced expression of CHI3L1 mRNA in the lung and with development of asthma (odds ratio (OR) 1.27; P = 0.036). The association was also observed following analysis of the three Japanese cohorts (OR 1.16; P = 0.013). A stronger association was found with late-onset asthma that developed at 41 years of age or later (OR 1.24; 95% confidence interval (CI) 1.07-1.45; P = 0.0058) and with a specific asthma phenotype characterized by late onset, less atopy, and mild airflow obstruction (OR 1.29; 95% CI 1.03-1.61; P = 0.027).The genotype consisting of the cis-eQTL allele that reduces expression of CHI3L1 was specifically associated with late-onset adult asthma. Given the important role of YKL-40 in many pathophysiological processes, including cell growth, migration, chemotaxis, reorganization, and tissue remodeling, it may be involved in an important pathogenic role in the establishment of inflammation and remodeling in asthmatic airways. Our findings may indicate the presence of a specific endotype related to exaggerated activation of YKL-40 in the pathogenesis of late-onset adult asthma.
Journal
-
- BMC Medical Genetics
-
BMC Medical Genetics 20 58-, 2019-04
BMC
- Tweet
Keywords
- Adult
- YKL-40
- Quantitative Trait Loci
- QH426-470
- Chitinase 3-like 1 (CHI3L1)
- Cohort Studies
- Japan
- Genetics
- Humans
- Chitinase-3-Like Protein 1
- Age of Onset
- Expression quantitative trait loci (eQTLs)
- Internal medicine
- Alleles
- Late-onset adult asthma
- RC31-1245
- Asthma
- Phenotype
- Case-Control Studies
- Research Article
- Genome-Wide Association Study
Details 詳細情報について
-
- CRID
- 1050564289151408640
-
- NII Article ID
- 120007127949
-
- NII Book ID
- AA12035063
-
- ISSN
- 14712350
-
- HANDLE
- 2241/00157114
-
- PubMed
- 30940096
-
- Text Lang
- en
-
- Article Type
- journal article
-
- Data Source
-
- IRDB
- Crossref
- CiNii Articles
- KAKEN
- OpenAIRE