Finding the Common Single-Nucleotide Polymorphisms in Three Autoimmune Diseases and Exploring Their Bio-Function by
Yen-Chang Chu1,2, Kuang-Hui Yu2,3, Wei-Tzu Lin4
1Department of Ophthalmology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan.
Biomedicines
|September 28, 2023
Summary
This study identifies shared genetic factors in Graves' ophthalmopathy (GO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Specific gene variants in CTLA4 show functional effects, suggesting a common genetic basis for these autoimmune diseases.
Area of Science:
- Immunogenetics
- Autoimmune Diseases
- Ophthalmology
Background:
- Autoimmune thyroid disease frequently co-occurs with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
- Eye-specific autoimmune conditions often correlate with systemic autoimmune diseases.
- Graves' ophthalmopathy (GO) is a common manifestation of Graves' disease with ocular involvement.
Purpose of the Study:
- To investigate the potential shared genetic background of Graves' ophthalmopathy (GO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE).
- To identify specific single-nucleotide polymorphisms (SNPs) associated with GO and shared across these three autoimmune conditions.
Main Methods:
- Genotyping analysis of co-stimulatory molecule genes in 40 GO patients and 40 healthy controls.
- Chi-square tests were employed to assess the association between SNPs and GO.
- Dual-luciferase reporter assays were used to confirm the bio-functional effects of identified SNPs.
Main Results:
- Several SNPs in CTLA4, CD28, PDCD1, and ICOS genes were significantly associated with GO.
- Six SNPs (rs11571315, rs733618, rs4553808, rs16840252, rs11571319, rs36084323) were found to be shared between GO, SLE, and RA.
- The T > C variant at rs733618 and A > G variant at rs4553808 in CTLA4 significantly reduced transcriptional activity.
Conclusions:
- This study provides the first evidence of shared genetically predisposing factors among Graves' ophthalmopathy, rheumatoid arthritis, and systemic lupus erythematosus.
- The identified functional variants rs733618 T > C and rs4553808 A > G in the CTLA4 gene may contribute to the pathogenesis of these diseases.
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