Cysteine-Altering NOTCH3 Variants Are Associated with an Increased Risk of Autoimmune Diseases

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 th...

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Bibliographic Details
Published in:Journal of clinical medicine Vol. 12; no. 19; p. 6278
Main Authors: Rieder, Emily, Li, Jiang, Rodriguez-Flores, Juan L., Taimur Malik, Muhammad, Abedi, Vida, Zand, Ramin
Format: Journal Article
Language:English
Published: Basel MDPI AG 29.09.2023
MDPI
Subjects:
Age
Amino acids
Antibodies
Antiphospholipid antibodies
Autoimmune diseases
Biobanks
Cellular signal transduction
Clinical medicine
Consent
Cysteine
Disease
Electronic health records
Genetic aspects
Genetic variation
Genomes
Health aspects
Immune system
Immunological research
Inflammation
Kinases
Laboratories
Medical records
Mutation
Peptides
Proteins
Risk factors
Thiols
Variables
United Kingdom
United Kingdom > UK
United States > US
ISSN:2077-0383, 2077-0383
Online Access:Get full text
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Summary: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.
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ISSN:2077-0383
2077-0383
DOI:10.3390/jcm12196278