| Title: | Association of Somatic TET2 Mutations With Giant Cell Arteritis |
| Journal: | Arthritis & Rheumatology |
| Published: | 2 Feb 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37909388/ |
| DOI: | https://doi.org/10.1002/art.42738 |
| Citations: | 3 (3 in last 2 years) as of 8 Aug 2024 |
Publication 8800
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
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.</p>
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.</p>
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).</p>
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.</p>
19 Authors
- Michelle L. Robinette
- Lachelle D. Weeks
- Ryan J. Kramer
- Mridul Agrawal
- Christopher J. Gibson
- Zhi Yu
- Aswin Sekar
- Arnav Mehta
- Abhishek Niroula
- Jared T. Brown
- Gregory C. McDermott
- Edith R. Reshef
- Jonathan E. Lu
- Victor D. Liou
- Carolina A. Chiou
- Pradeep Natarajan
- Suzanne K. Freitag
- Deepak A. Rao
- Benjamin L. Ebert
1 Application
| Application ID | Title |
|---|---|
| 50834 | Identifying the regulators of clonal hematopoiesis of indeterminate potential (CHIP) |
Enabling scientific discoveries that improve human health