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

Abstract

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.

Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis

“…Previous studies have demonstrated that biomarkers including NEK7 [431], BMI1 [410], CAV1 [433], TRIB3 [414], SRF (serum response factor) [822], STAT1 [823], and TP53 [824] are believed to be related to the occurrence of IPF. Biomarkers including NEK7 [656], CAV1 [658], TSGA10 [665], STAT1 [825], TP53 [826], and NFKB1 [827] are reported to be associated with systemic lupus erythematosus. Biomarkers including NEK7 [686] and CAV1 [689] were associated with the risk of pneumonia.…”

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

“…Previous studies have demonstrated that NEK7 [431], BMI1 [410], CAV1 [433], TRIB3 [414], SRF (serum response factor) [822], STAT1 [823] and TP53 [824] are an independent prognostic factors in IPF and might be associated with IPF pathogenesis. NEK7 [656], CAV1 [658], TSGA10 [665], STAT1 [825], TP53 [826] and NFKB1 [827] are associated with systemic lupus erythematosus. NEK7 [686] and CAV1 [689] were an important participant in pneumonia.…”