| Title: | Cysteine-Altering NOTCH3 Variants Are Associated with an Increased Risk of Autoimmune Diseases |
| Journal: | Journal of Clinical Medicine |
| Published: | 29 Sep 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37834922/ |
| DOI: | https://doi.org/10.3390/jcm12196278 |
| URL: | https://www.mdpi.com/2077-0383/12/19/6278/pdf?version=1695970397 |
Publication 9451
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Abstract
Autoimmune conditions have been reported among patients with cysteine-altering NOTCH3 variants and CADASIL. This study aimed to investigate the occurrence of autoimmune illnesses and markers of inflammation in such populations. Cases were identified who had a NOTCH3 cysteine-altering variant from the Geisinger MyCode® Community Health Initiative (MyCode®). We further performed external validation using the UK Biobank cohort. A cohort of 121 individuals with a NOTCH3 cysteine-altering variant from MyCode® was compared to a control group with no non-synonymous variation in NOTCH3 (n = 184). Medical records were evaluated for inflammatory markers and autoimmune conditions, which were grouped by the organ systems involved. A similar analysis was conducted using data from the UK Biobank (n~450,000). An overall increase in inflammatory markers among participants with a NOTCH3 cysteine-altering variant was observed when compared to an age- and sex-matched MyCode® control group (out of participants with laboratory testing: 50.9% versus 26.7%; p = 0.0047; out of total participants: 23.1% versus 10.9%; p = 0.004). Analysis of UK Biobank data indicated any autoimmune diagnosis (1.63 [1.14, 2.09], p= 2.665 × 10-3) and multiple sclerosis (3.42 [1.67, 6.02], p = 9.681 × 10-4) are associated with a NOTCH3 cysteine-altering variant in any domain. Our findings suggest a possible association between NOTCH3 cysteine-altering variants and autoimmune conditions.</p>
6 Authors
- Emily Rieder
- Jiang Li
- Juan L. Rodriguez-Flores
- Muhammad Taimur Malik
- Vida Abedi
- Ramin Zand
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