University of Oulu

Hollmén, M., Laaka, A., Partanen, J.J. et al. KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis. Respir Res 24, 240 (2023).

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)
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Language: English
Published: Springer Nature, 2023
Publish Date: 2023-10-09


Background: 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.

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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
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
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.
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