Rare Variants in Systemic Lupus Erythematosus: From Monogenic to Polygenic Disease
Main Article Content
Abstract
The clinical and genotypic characterization of autoimmune diseases, including systemic lupus erythematosus (SLE), has made great strides recently as a result of tremendous advancements in gene sequencing technologies. Systemic lupus erythematosus is a complex multisystem disease characterized by high clinical variability due to abnormalities in both the innate and adaptive immune systems. Several genetic variants as well as environmental and hormonal factors have been identified, but the etiology of lupus is not fully understood yet. The ability of genome-wide association studies to scan thousands of individuals has enabled researchers to associate thousands of common variants to lupus. Common polymorphisms may jointly predispose to lupus, but their individual impact on the disease is minimal. It's becoming progressively more evident that rare mutations have a far higher influence. The role of rare variation in lupus has been the subject of intense research. Several approaches including genotyped-based follow-up of the variants in families, hierarchical screening, and imputation, have been applied to elucidate their functional involvement. Nevertheless, due to their rarity and the absence of standardized methodology, rare variants are still challenging to study.
Most lupus patients present a polygenic form of the disease, which is defined by the complex interplay between genetic and environmental factors. Still, certain lupus patients and patients with lupus-like phenotypes might be affected by monogenic lupus, a group of disorders largely caused by individual gene mutation abnormalities. Although monogenic lupus is rare, it has been associated with a sizable number of genes in a range of pathways, mostly resulting in early-onset phenotypes. The study of rare variants causing monogenic lupus has resulted in incredibly useful breakthroughs in our understanding of the function of rare variants in the disease, nonetheless further research is still required.
Keywords:
Systemic Erythematosus Lupus, SLE, monogenic lupus, polygenic lupus, rare variants
Article Details
How to Cite
ALARCÓN-RIQUELME, Marta E.; RODRÍGUEZ, Ruth D..
Rare Variants in Systemic Lupus Erythematosus: From Monogenic to Polygenic Disease.
Medical Research Archives, [S.l.], v. 11, n. 10, oct. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4363>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i10.4363.
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Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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10. Almlöf JC, Nystedt S, Leonard D, et al. Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus. Hum Genet. 2019;138(2):141-150. doi:10.1007/s00439-018-01966-7
11. Jiang SH, Stanley M, Vinuesa CG. Rare genetic variants in systemic autoimmunity. Immunol Cell Biol. 2020;98(6):490-499. doi:10.1111/imcb.12339
12. Martínez-Bueno M, Alarcón-Riquelme ME. Exploring Impact of Rare Variation in Systemic Lupus Erythematosus by a Genome Wide Imputation Approach. Front Immunol. 2019;10. doi:10.3389/fimmu.2019.00258
13. Saint Pierre A, Génin E. How important are rare variants in common disease? Brief Funct Genomics. 2014;13(5):353-361. doi:10.1093/bfgp/elu025
14. Alperin JM, Ortiz-Fernández L, Sawalha AH. Monogenic Lupus: A Developing Paradigm of Disease. Front Immunol. 2018;9:2496. doi:10.3389/fimmu.2018.02496
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