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KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis |
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| Author: | Hollmén, Maria1; Laaka, Atte1; Partanen, Juulia J.2; |
| Organizations: |
1Individrug, Heart and Lung Centre, The University of Helsinki and Helsinki University Hospital, Research Programs Unit, Helsinki, Finland 2Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland 3Research Unit of Biomedicine and Internal Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 1 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe20231009139315 |
| Language: | English |
| Published: |
Springer Nature,
2023
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| Publish Date: | 2023-10-09 |
| Description: |
AbstractBackground: Idiopathic pulmonary fibrosis (IPF) has an unknown aetiology and limited treatment options. A recent meta-analysis identified three novel causal variants in the TERT, SPDL1, and KIF15 genes. This observational study aimed to investigate whether the aforementioned variants cause clinical phenotypes in a well-characterised IPF cohort. Methods: The study consisted of 138 patients with IPF who were diagnosed and treated at the Helsinki University Hospital and genotyped in the FinnGen FinnIPF study. Data on > 25 clinical parameters were collected by two pulmonologists who were blinded to the genetic data for patients with TERT loss of function and missense variants, SPDL1 and KIF15 missense variants, and a MUC5B variant commonly present in patients with IPF, or no variants were separately analysed. Results: The KIF15 missense variant is associated with the early onset of the disease, leading to progression to early-age transplantation or death. In patients with the KIF15 variant, the median age at diagnosis was 54.0 years (36.5–69.5 years) compared with 72.0 years (65.8–75.3 years) in the other patients (P = 0.023). The proportion of KIF15 variant carriers was 9- or 3.6-fold higher in patients aged < 55 or 65 years, respectively. The variants for TERT and MUC5B had similar effects on the patient’s clinical course, as previously described. No distinct phenotypes were observed in patients with the SPDL1 variant. Conclusions: Our study indicated the potential of KIF15 to be used in the genetic diagnostics of IPF. Further studies are needed to elucidate the biological mechanisms of KIF15 in IPF. see all
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| Series: |
Respiratory research |
| ISSN: | 1465-9921 |
| ISSN-E: | 1465-9921 |
| ISSN-L: | 1465-9921 |
| Volume: | 24 |
| Article number: | 240 |
| DOI: | 10.1186/s12931-023-02540-0 |
| OADOI: | https://oadoi.org/10.1186/s12931-023-02540-0 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3121 General medicine, internal medicine and other clinical medicine |
| Subjects: | |
| Funding: |
Open Access funding provided by University of Helsinki including Helsinki University Central Hospital. This study was funded by the University of Helsinki, Helsinki University Hospital Funds, Nummela Sanatorium, the Finnish TB-Foundation, the Finnish Research Foundation of the Pulmonary Diseases, Academy of Finland, the doctoral program in population health, university of Helsinki, and Boehringer Ingelheim. Funding was used for data acquisition and to assist staff. The researchers in this study did not receive additional salaries or payments, apart from those from the research institutions where they were employed. The funding sources played no role in the study design, data collection, analysis, and interpretation, or writing of the manuscript. The corresponding author has access to all the data in the study and has the final responsibility for the decision to submit the manuscript. The data presented are owned by two organisations, the University of Helsinki and the Helsinki University Hospital, and access is granted with research permission from these organisations. |
| Copyright information: |
© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
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https://creativecommons.org/licenses/by/4.0/ |