KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis
Abstract 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 c...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-023-02540-0 |
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| author | Maria Hollmén Atte Laaka Juulia J. Partanen Jukka Koskela Eva Sutinen Riitta Kaarteenaho Mari Ainola Marjukka Myllärniemi |
| author_facet | Maria Hollmén Atte Laaka Juulia J. Partanen Jukka Koskela Eva Sutinen Riitta Kaarteenaho Mari Ainola Marjukka Myllärniemi |
| author_sort | Maria Hollmén |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T14:58:56Z |
| format | Article |
| id | doaj.art-46801aba31874d1798b87c4c16084b5d |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-09T14:58:56Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-46801aba31874d1798b87c4c16084b5d2023-11-26T14:01:48ZengBMCRespiratory Research1465-993X2023-09-012411910.1186/s12931-023-02540-0KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosisMaria Hollmén0Atte Laaka1Juulia J. Partanen2Jukka Koskela3Eva Sutinen4Riitta Kaarteenaho5Mari Ainola6Marjukka Myllärniemi7Individrug, Heart and Lung Centre, The University of Helsinki and Helsinki University Hospital, Research Programs UnitIndividrug, Heart and Lung Centre, The University of Helsinki and Helsinki University Hospital, Research Programs UnitInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiIndividrug, Heart and Lung Centre, The University of Helsinki and Helsinki University Hospital, Research Programs UnitResearch Unit of Biomedicine and Internal Medicine, University of Oulu and Oulu University HospitalIndividrug, Heart and Lung Centre, The University of Helsinki and Helsinki University Hospital, Research Programs UnitIndividrug, Heart and Lung Centre, The University of Helsinki and Helsinki University Hospital, Research Programs UnitAbstract 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.https://doi.org/10.1186/s12931-023-02540-0Idiopathic pulmonary fibrosisKIF15TERTSPDL1Missense variant |
| spellingShingle | Maria Hollmén Atte Laaka Juulia J. Partanen Jukka Koskela Eva Sutinen Riitta Kaarteenaho Mari Ainola Marjukka Myllärniemi KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis Respiratory Research Idiopathic pulmonary fibrosis KIF15 TERT SPDL1 Missense variant |
| title | KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis |
| title_full | KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis |
| title_fullStr | KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis |
| title_full_unstemmed | KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis |
| title_short | KIF15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis |
| title_sort | kif15 missense variant is associated with the early onset of idiopathic pulmonary fibrosis |
| topic | Idiopathic pulmonary fibrosis KIF15 TERT SPDL1 Missense variant |
| url | https://doi.org/10.1186/s12931-023-02540-0 |
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