التفاصيل البيبلوغرافية
| العنوان: |
Association of Somatic TET2 Mutations With Giant Cell Arteritis |
| المؤلفون: |
Robinette, Michelle L., Weeks, Lachelle D., Kramer, Ryan J., Agrawal, Mridul, Gibson, Christopher J., Yu, Zhi, Sekar, Aswin, Mehta, Arnav, Niroula, Abhishek, Brown, Jared T., McDermott, Gregory C., Reshef, Edith R., Lu, Jonathan E., Liou, Victor D., Chiou, Carolina A., Natarajan, Pradeep, Freitag, Suzanne K., Rao, Deepak A., Ebert, Benjamin L. |
| المساهمون: |
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Burroughs Wellcome Fund, Deutsche Forschungsgemeinschaft, Doris Duke Charitable Foundation, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Edward P. Evans Foundation, Howard Hughes Medical Institute, Knut och Alice Wallenbergs Stiftelse, Sarnoff Cardiovascular Research Foundation |
| المصدر: |
Arthritis & Rheumatology ; volume 76, issue 3, page 438-443 ; ISSN 2326-5191 2326-5205 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2024 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
Objective Giant cell arteritis (GCA) is an age‐related vasculitis. Prior studies have identified an association between GCA and hematologic malignancies (HMs). How the presence of somatic mutations that drive the development of HMs, or clonal hematopoiesis (CH), may influence clinical outcomes in GCA is not well understood. Methods To examine an association between CH and GCA, we analyzed sequenced exomes of 470,960 UK Biobank (UKB) participants for the presence of CH and used multivariable Cox regression. To examine the clinical phenotype of GCA in patients with and without somatic mutations across the spectrum of CH to HM, we performed targeted sequencing of blood samples and electronic health record review on 114 patients with GCA seen at our institution. We then examined associations between specific clonal mutations and GCA disease manifestations. Results UKB participants with CH had a 1.48‐fold increased risk of incident GCA compared to UKB participants without CH. GCA risk was highest among individuals with cytopenia (hazard ratio [HR] 2.98, P = 0.00178) and with TET2 mutation (HR 2.02, P = 0.00116). Mutations were detected in 27.2% of our institutional GCA cohort, three of whom had HM at GCA diagnosis. TET2 mutations were associated with vision loss in patients with GCA (odds ratio 4.33, P = 0.047). Conclusions CH increases risk for development of GCA in a genotype‐specific manner, with the greatest risk being conferred by the presence of mutations in TET2 . Somatic TET2 mutations likewise increase the risk of GCA‐associated vision loss. Integration of somatic genetic testing in GCA diagnostics may be warranted in the future. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1002/art.42738 |
| الإتاحة: |
https://doi.org/10.1002/art.42738Test |
| حقوق: |
http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.10653E26 |
| قاعدة البيانات: |
BASE |
