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

被引:3
作者
Macedo, Jacyara Maria Brito [1 ]
Silva, Amanda Lima [1 ]
Pinto, Amanda Chaves [1 ]
Landeira, Leandro Ferreira Lopes [1 ]
Portari, Elyzabeth Avvad [2 ,3 ]
Santos-Reboucas, Cintia Barros [2 ]
Klumb, Evandro Mendes [4 ]
机构
[1] State Univ Rio de Janeiro UERJ, Dept Biochem, Rio De Janeiro, Brazil
[2] State Univ Rio de Janeiro UERJ, Dept Pathol Anat, Rio De Janeiro, Brazil
[3] Fiocruz MS, Fernandes Figueira Inst, Dept Pathol, Rio De Janeiro, Brazil
[4] State Univ Rio de Janeiro UERJ, Pedro Ernesto Univ Hosp, Dept Rheumatol, Blvd 28 Setembro,87,Vila Isabel, BR-20551030 Rio De Janeiro, RJ, Brazil
关键词
Systemic lupus erythematosus; Genetic polymorphisms; TP53; p21; ACTIVATED/MEMORY T-CELLS; P53; CODON-72; ASSOCIATION; GENE; SUSCEPTIBILITY; AUTOIMMUNE; PATHOGENESIS; DEFICIENCY; APOPTOSIS; ARTHRITIS;
D O I
10.1186/s42358-023-00320-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundThe 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.MethodsGenotyping 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.ResultsProtective 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).ConclusionsOur 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.
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页数:13
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