Evidence map›Paper›PMID 30940096›Full record

ArticleBMC medical genetics2019

A cis-eQTL allele regulating reduced expression of CHI3L1 is associated with late-onset adult asthma in Japanese cohorts.

Jun Kanazawa, Haruna Kitazawa, Hironori Masuko, Yohei Yatagai, Tohru Sakamoto, Yoshiko Kaneko, Hiroaki Iijima, Takashi Naito, Takefumi Saito, Emiko Noguchi and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medical genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 38% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Omics for the future in asthma.Seminars in immunopathology · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 1 country.

Jun KanazawaDepartment of Pulmonary Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan.
Haruna KitazawaDepartment of Pulmonary Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan.
Hironori MasukoDepartment of Pulmonary Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan. hmasuko@md.tsukuba.ac.jp.ORCID 0000-0002-5917-7973
Yohei YatagaiDepartment of Pulmonary Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan.
Tohru SakamotoDepartment of Pulmonary Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan.
Yoshiko KanekoDepartment of Pulmonary Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan.
Hiroaki IijimaTsukuba Medical Center, Amakubo 1-3-1, Tsukuba, Ibaraki, 305-8558, Japan.
Takashi NaitoTsukuba Medical Center, Amakubo 1-3-1, Tsukuba, Ibaraki, 305-8558, Japan.
Takefumi SaitoNational Hospital Organization Ibaraki Higashi National Hospital, Terunuma 825, Tokai, Ibaraki, 319-1113, Japan.
Emiko NoguchiDepartment of Medical Genetics, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan.
Satoshi KonnoDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita15, Nishi7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.
Masaharu NishimuraDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita15, Nishi7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.
Tomomitsu HirotaResearch Center for Medical Science, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
Mayumi TamariResearch Center for Medical Science, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
Nobuyuki HizawaDepartment of Pulmonary Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan.
University of Tsukuba · JPHokkaido University · JPJikei University School of Medicine · JPTsukuba Medical Center Hospital · JPNational Hospital Organization · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe 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.

methodsThis 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.

resultsIn 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).

conclusionsThe 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.

Indexed as

Age of OnsetAllelesQuantitative Trait LociAdultAsthmaCase-Control StudiesChitinase-3-Like Protein 1Cohort StudiesGenome-Wide Association StudyHumansJapanPhenotypeCHI3L1 protein, humanChitinase-3-Like Protein 1AsthmaChitinase 3-like 1 (CHI3L1)Expression quantitative trait loci (eQTLs)GeneticsLate-onset adult asthmaYKL-40

Identifiers

PMID30940096
PMCPMC6444873
OpenAlexW2944297063

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.