TP53 and p21 (CDKN1A) polymorphisms and the risk of systemic lupus erythematosus.

Autor: Macedo JMB; Department of Biochemistry, State University of Rio de Janeiro - UERJ, Rio de Janeiro, Brazil., Silva AL; Department of Biochemistry, State University of Rio de Janeiro - UERJ, Rio de Janeiro, Brazil., Pinto AC; Department of Biochemistry, State University of Rio de Janeiro - UERJ, Rio de Janeiro, Brazil., Landeira LFL; Department of Biochemistry, State University of Rio de Janeiro - UERJ, Rio de Janeiro, Brazil., Portari EA; Department of Pathological Anatomy, State University of Rio de Janeiro - UERJ, Rio de Janeiro, Brazil.; Department of Pathology, Fernandes Figueira Institute - FIOCRUZ, Rio de Janeiro, Brazil., Santos-Rebouças CB; Department of Pathological Anatomy, State University of Rio de Janeiro - UERJ, Rio de Janeiro, Brazil., Klumb EM; Department of Rheumatology, Pedro Ernesto University Hospital, State University of Rio de Janeiro - UERJ, Boulevard 28 de Setembro, 87, Vila Isabel, Rio de Janeiro, RJ, CEP 20551-030, Brazil. klumb@uol.com.br.
Jazyk: angličtina
Zdroj: Advances in rheumatology (London, England) [Adv Rheumatol] 2023 Aug 21; Vol. 63 (1), pp. 43. Date of Electronic Publication: 2023 Aug 21.
DOI: 10.1186/s42358-023-00320-4
Abstrakt: Background: The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C-rs1042522; p53 PIN3-rs17878362; p21 31 C > A-rs1801270; p21 70 C > T-rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population.
Methods: Genotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis.
Results: Protective effect was observed for the genotype combinations p53 PIN3 A1/A1-p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively).
Conclusions: Our findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients.
(© 2023. Sociedade Brasileira de Reumatologia.)
Databáze: MEDLINE
Externí odkaz: