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. Highlights The polymorphisms TP53 rs1042522 (G > C) and TP53 rs17878362 (16 bp Del/Ins) were associated with SLE risk in whites. In whites, the combined genotype TP53 rs1042522 GC- TP53 rs17878362 A1A2 and the haplotype TP53 rs1042522 C-rs17878362 A2 represented higher SLE risk. Combination of TP53 rs17878362 (16 bp Del/Ins) and p21 rs1801270 (C > A) protected against SLE in non-white women. TP53 and p21 (CDKN1A) polymorphisms may be SLE susceptibility markers for specific groups. p p5 p2 diseases SLE. . functions TP TP5 CDKN1A CDKNA CDKN A (CDKN1A (p5 7 Crs1042522 Crs rs C—rs1042522 PIN3rs17878362 PINrs PIN PIN3—rs17878362 3 Ars1801270 Ars A—rs1801270 Trs1059234 Trs T rs1059234 T—rs1059234 (SLE 35 cases, cases (cases 145 controls 208 reaction andor or sequencing analysis A1A1 AA A1 A1/A -p2 CA C/A 0.45, 045 0.45 , 0 45 0.45) A1/A2p21 A1A2p21 AAp A1/A2-p2 CC nonwhite non white 0.28. 028 0.28 28 0.28) Whites Ccontaining containing 3.06 306 06 A2containing Acontaining 6.93 693 6 93 G/Cp53 GCp53 GCp G/C G/C-p5 9.00. 900 9.00 9 00 9.00) Further 2.82, 282 2.82 2 82 2.82) A2A2 A2/A 469 4 69 4.6 334 34 3.34 respectively. respectively respectively) rs104252 rs1787836 16 (1 Del/Ins DelIns Del Ins whites GC A1A Crs17878362 C-rs1787836 rs180127 (p Crs104252 C—rs104252 PIN3rs1787836 PIN3—rs1787836 Ars180127 A—rs180127 Trs105923 rs105923 T—rs105923 14 20 -p 04 0.4 A2p21 A1/A2p2 A1A2p2 A1/A2-p 02 0.2 3.0 30 6.9 Cp53 Cp G/Cp5 GCp5 G/C-p 90 9.0 2.8 8 A2A 46 4. 33 3.3 rs10425 rs178783 1 ( Crs1787836 C-rs178783 rs18012 Crs10425 C—rs10425 PIN3rs178783 PIN3—rs178783 Ars18012 A—rs18012 Trs10592 rs10592 T—rs10592 0. Ap A2p2 A1/A2p A1A2p 3. 6. Cp5 G/Cp 9. 2. rs1042 rs17878 Crs178783 C-rs17878 rs1801 Crs1042 C—rs1042 PIN3rs17878 PIN3—rs17878 Ars1801 A—rs1801 Trs1059 rs1059 T—rs1059 A2p rs104 rs1787 Crs17878 C-rs1787 rs180 Crs104 C—rs104 PIN3rs1787 PIN3—rs1787 Ars180 A—rs180 Trs105 rs105 T—rs105 rs10 rs178 Crs1787 C-rs178 rs18 Crs10 C—rs10 PIN3rs178 PIN3—rs178 Ars18 A—rs18 Trs10 T—rs10 rs1 rs17 Crs178 C-rs17 Crs1 C—rs1 PIN3rs17 PIN3—rs17 Ars1 A—rs1 Trs1 T—rs1 Crs17 C-rs1 C—rs PIN3rs1 PIN3—rs1 A—rs T—rs C-rs PIN3rs PIN3—rs

RESUMO Objetivo: Investigar potenciais associações de quatro substituições do gene NAT2 (N-acetiltransferase 2) e do fenótipo acetilador de NAT2 com o lúpus eritematoso sistêmico (LES) e os fenótipos clínicos. Métodos: A análise molecular das substituições 481C > T, 590G > A, 857G > A e 191G > A do gene NAT2 foi feita com a técnica de PCR-RFLP, usando DNA extraído de amostras de sangue periférico obtidas de pacientes com LES (n = 91) e controles (n = 97). Resultados e conclusões: O genótipo 857GA foi mais prevalente entre pacientes com LES não brancas (OR = 4,01, IC 95% = 1,18-13,59). O alelo 481 T apresentou associação positiva com as alterações hematológicas que envolvem mecanismos autoimunes, especificamente anemia hemolítica autoimune ou trombocitopenia autoimune (OR = 1,97; IC 95% = 1,01-3,81).

ABSTRACT Objective: To investigate potential associations of four substitutions in NAT2 gene and of acetylator phenotype of NAT2 with systemic lupus erythematosus (SLE) and clinical phenotypes. Methods: Molecular analysis of 481C>T, 590G>A, 857G>A, and 191G>A substitutions in the NAT2 gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, from DNA extracted from peripheral blood samples obtained from patients with SLE (n = 91) and controls (n = 97). Results and conclusions: The 857GA genotype was more prevalent among nonwhite SLE patients (OR = 4.01, 95% CI = 1.18-13.59). The 481T allele showed a positive association with hematological disorders that involve autoimmune mechanisms, specifically autoimmune hemolytic anemia or autoimmune thrombocytopenia (OR = 1.97; 95% CI = 1.01-3.81).