Evidence map›Paper›PMID 41174729›Full record

ArticleRespiratory research2025

Gene variants of interferon induced with helicase C domain 1 in Japanese patients with Dermatomyositis-associated rapidly progressive interstitial lung disease: a genetic association study using whole-exome and Sanger sequencing.

Masaki Okamoto, Akira Yoshida, Yoshiaki Zaizen, Motoko Ishida, Toshimasa Shimizu, Noriho Sakamoto, Hironao Hozumi, Yasuhiko Yamano, Takahisa Gono, Norikazu Matsuo and 9 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

19 authors.

Masaki OkamotoDivision of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi- machi, Kurume, Fukuoka, 830-0011, Japan. okamoto_masaki@med.kurume-u.ac.jp.
Akira YoshidaDepartment of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
Yoshiaki ZaizenDivision of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi- machi, Kurume, Fukuoka, 830-0011, Japan.
Motoko IshidaDepartment of Rheumatology, NHO Kyushu Medical Center, 1-8-1 Jigyouhama, Chuo-ku, Fukuoka, 810-8563, Japan.
Toshimasa ShimizuDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Noriho SakamotoDepartment of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Hironao HozumiSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1- 20-1 Handayama, Higashi-ku, Hamamatsu, Sizuoka, 431-3192, Japan.
Yasuhiko YamanoDepartment of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake, Seto, 489-8642, Japan.
Takahisa GonoDepartment of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
Norikazu MatsuoDivision of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi- machi, Kurume, Fukuoka, 830-0011, Japan.
Shinjiro KaiedaDivision of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi- machi, Kurume, Fukuoka, 830-0011, Japan.
Masataka KuwanaDepartment of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
Tomoya MiyamuraDepartment of Rheumatology, NHO Kyushu Medical Center, 1-8-1 Jigyouhama, Chuo-ku, Fukuoka, 810-8563, Japan.
Atsushi KawakamiDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Hiroshi MukaeDepartment of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Takafumi SudaSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1- 20-1 Handayama, Higashi-ku, Hamamatsu, Sizuoka, 431-3192, Japan.
Yasuhiro KondohDepartment of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake, Seto, 489-8642, Japan.
Ken YamamotoDepartment of Medical Biochemistry, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan. yamamoto_ken@med.kurume-u.ac.jp.
Tomoaki HoshinoDivision of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi- machi, Kurume, Fukuoka, 830-0011, Japan. hoshino@med.kurume-u.ac.jp.

Funding

Grant-in-Aid for Scientific Research (C) 22K08274
6 · The paper itself

Abstract

backgroundPatients with Dermatomyositis (DM) having anti-melanoma differentiation-associated gene 5 (MDA5) antibodies occasionally develop rapidly progressive interstitial lung disease (RP-ILD), a serious inflammatory complication; however, no genetic biomarker has yet been identified for this condition. This study aimed to identify interferon-induced with helicase C domain 1 (also known as MDA5) gene (IFIH1) variants associated with a high risk of DM-associated RP-ILD.

methodsA total of 204 patients with DM were enrolled from six institutions. Whole-exome sequencing was performed on nine patients with DM-associated interstitial lung disease (ILD) who were positive for anti-MDA5 antibodies, and six single-nucleotide polymorphisms (SNPs) were identified: p.Val194Ala (no reference SNP ID), rs1990760, rs3747517, rs12479043, rs10930046, and rs141134657. Allele frequencies of eight IFIH1 variants-including these six SNPs plus rs117608083 and rs183412282-were analyzed using Sanger sequencing. Statistical analyses included allele frequency comparisons and genotype-based assessments (dominant and recessive models), and the Armitage trend test.

resultsAmong the 204 patients with DM, 109 (53.4%) had classic DM and 95 (46.6%) had clinically amyopathic DM. A total of 174 patients (85.3%) had ILD, and 62 (30.4%) were positive for anti-MDA5 antibodies. Among the 204 patients with DM, low minor allele frequencies (MAFs) for rs12479043 and rs10930046 were significantly (p < 0.05) associated with high rates of ILD and anti-MDA5 antibodies. Among the 174 patients with ILD, a low MAF for rs141134657 was significantly (p < 0.05) associated with a high incidence of acute onset of ILD within 3 months, in accordance with allele, genotype, and Armitage trend tests, but not the recessive model. A low MAF for rs141134657 tended to be associated with high serum C-reactive protein levels in accordance with the additive and dominant models, but the result was not significant. None of the analyzed IFIH1 variants were significantly associated with serum levels of ferritin, KL-6, and lactate dehydrogenase.

conclusionThis study identified genetic biomarkers associated with the risk of RP-ILD in patients with DM. These findings suggest that analysis of IFIH1 variants may serve as a valuable tool for predicting the development of RP-ILD in this patient population.

Indexed as

DermatomyositisDisease ProgressionExome SequencingGenetic Association StudiesGenetic VariationInterferon-Induced Helicase, IFIH1Lung Diseases, InterstitialPolymorphism, Single NucleotideAdultAgedEast Asian PeopleFemaleHumansJapanMaleMiddle AgedIFIH1 protein, humanInterferon-Induced Helicase, IFIH1Genetic biomarkerIdiopathic inflammatory myopathiesMelanoma differentiation-associated gene 5Rapid progressive interstitial lung diseaseSanger sequencing

Identifiers

PMID41174729
PMCPMC12577163

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.