Genetic and Environmental Contributions to Systemic Sclerosis: Current Evidence and Future Directions in Precision Disease Profiling
DOI:
https://doi.org/10.64149/J.Carcinog.24.10s.684-695Keywords:
scleroderma, systemic sclerosis, genetics, GWAS, risk factors, autoimmunity, inflammationAbstract
Systemic sclerosis (SSc) is a complex autoimmune disease characterized by connective tissue involvement and a diverse array of clinical manifestations. The pathophysiology of SSc, which encompasses systemic sclerosis and localized scleroderma, remains incompletely understood. This review provides an overview of the genetic and environmental factors implicated in the development of SSc, as well as the advancements in scientific methods utilized to study the disease.
Genetic factors, particularly human leukocyte antigen (HLA) genes within the major histocompatibility complex (MHC) region, have been extensively linked to susceptibility to SSc. Research has identified specific HLA alleles, including HLA-DPB1 and HLA-DRB1, to be associated with distinct clinical subsets and autoimmune responses in different ethnic populations. Additionally, non-HLA genes, such as IRF5, STAT4, IL12, IL12RB, CD247, PRDM1, TNFAIP3, TNIP1, CSK, and GSDMA, have been implicated in SSc susceptibility and pathogenesis.
Environmental factors, including food contaminants, silica dust, and certain drugs, are known to contribute to the onset of SSc. The interplay between genetic susceptibility and environmental influences emphasizes the multifactorial nature of SSc etiology.
Scientific methods, such as genome-wide association studies (GWAS) and genomic risk scores, have provided insights into the genetic basis of SSc and its subtypes. These methods have aided in identifying specific genetic variations associated with SSc development, helping to elucidate the complex interplay of genes involved in immune regulation and inflammatory responses.
In conclusion, a comprehensive understanding of the genetic and environmental factors, as well as the scientific methods used in SSc studies, is essential for advancing the diagnosis, prognosis, and treatment of SSc, ultimately leading to improved clinical outcomes for individuals affected by this debilitating autoimmune disease.
