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. 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.

Differences in HPV infection and HPV-related lesions between the cervix and anus in hiv-positive women / Diferenças na infecção por HPV e lesões HPV-relacionadas entre colo uterino e ânus em mulheres hiv positivas

Introduction: the prevalence of cervical and anal human papillomavirus (HPV) infection in women infected with human immunodeficiency virus (HIV) is high. However, little is known about the differences in the susceptibility of these infections and related lesions. The aim of this study was to describe the association between the prevalence of cervical and anal HPV infection and HPV-related lesions in HIV-positive women. Methods: this study included 88 HIV-positive women attending an outpatient clinic in a university hospital. Ectocervical, endocervical, and anal samples were collected for colpocytology and anal cytology. A polymerase chain reaction-based technique was used to detect HPV deoxyribonucleic acid in endocervical and anal swab samples. Results: the cervical and anal HPV positivity rates were 35.21% and 78.8%, respectively. The presence of HPV-related lesions on colpocytology was associated with anal HPV positivity (P = 0.027). The ratio between cervical HPV infection and cervical HPV-related lesions was 2.5. The ratio between anal HPV infection and anal HPV-related lesions was 4.3. Overall, 30% had concomitant HPV DNA in the cervix and anus. Conclusion: there are differences in the susceptibility of infections and related lesions between the cervix and anus. Despite a higher incidence of anal HPV, the progression to HPV-related lesion does not occur via the same manner in the cervix and anus. Moreover, cervical HPV-related lesions in HIV-positive women may serve as a cue for anal preventive strategies, and further investigations in these women may be useful.

Introdução: as infecções cervicais e anais pelo papilomavírus humano (HPV) em mulheres infectadas com o vírus da imunodeficiência umana (HIV) são muito prevalentes. Entretanto, pouco se sabe sobre as diferenças na suscetibilidade entre essas infecções e as lesões HPV-relacionadas. Objetivo: descrever a associação entre as prevalências de infecção cervical e anal pelo HPV e lesões relacionadas em mulheres HIV-positivas. Metodologia: este estudo incluiu 88 mulheres HIV-positivas atendidas em ambulatório de hospital universitário. Amostras ectocervicais, endocervicais e anais foram coletadas para colpocitologia e citologia anal. Uma técnica baseada na reação em cadeia da polimerase foi usada para detectar o ácido desoxirribonucléico (DNA) do HPV em amostras de swabs endocervical e anal. Resultado: as taxas de positividade do HPV cervical e anal foram de 35,21% e 78,8%, respectivamente. As lesões relacionadas ao HPV na colpocitologia foram associadas à positividade anal para o HPV (P = 0,027). A proporção entre infecção cervical por HPV e lesões cervicais relacionadas foi de 2,5. A proporção entre a infecção anal por HPV e as lesões anais relacionadas foi de 4,3. 30% tinham DNA-HPV concomitante no colo do útero e ânus. Conclusão: existem diferenças na suscetibilidade de infecções e de lesões relacionadas entre o colo e o ânus. Apesar de maior incidência de HPV anal, a progressão para lesões relacionadas não ocorre da mesma forma no colo e no ânus. Além disso, lesões cervicais relacionadas ao HPV em mulheres HIV positivas podem servir como pista para estratégias preventivas anais. Investigações adicionais podem ser úteis.

Polymorphisms in NAT2 (N-acetyltransferase 2) gene in patients with systemic lupus erythematosus / Polimorfismos no gene NAT2 (N-acetiltransferase 2) em pacientes com lúpus eritematoso sistêmico

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).

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).