RESUMO
BACKGROUND: Vitiligo is a pigmentation disorder of autoimmune aetiology. Polymorphisms in beta-defensin genes have been linked to a predisposition to some autoimmune disorders. AIM: To evaluate the role of polymorphisms in DEFB1, the gene encoding for human beta-defensin (HBD)-1 and its 5' untranslated region in nonsegmental vitiligo. METHODS: In total, 354 participants [171 patients with non-segmental vitiligo and 183 age and sex-matched healthy controls (HCs)], were genotyped by the PCR-restriction fragment length polymorphism (RFLP) method. For 80 of these individuals (40 patients and -40 HCs) serum HBD-1 was also measured by ELISA. RESULTS: The -44 G allele, CG genotype and GGG haplotype increased the risk for vitiligo (P < 0.02 in all cases), whereas the -20 AA genotype seems to be protective (P = 0.04). Serum HBD-1 levels were lower in patients with vitiligo than in HCs (P < 0.01), as well as in patients with active vitiligo compared with those with stable vitiligo and with HCs (P < 0.05 in both cases), CONCLUSION: Our results suggest that HBD-1 and its gene polymorphisms may modulate vitiligo susceptibility and/or disease activity. This is the first report, to our knowledge, of the association of serum HBD-1 levels and DEFB1 gene polymorphisms with vitiligo.
Assuntos
Estudos de Associação Genética/métodos , Polimorfismo de Nucleotídeo Único , Vitiligo/genética , beta-Defensinas/genética , Regiões 5' não Traduzidas , Adolescente , Adulto , Idade de Início , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Polimorfismo de Fragmento de Restrição , Índice de Gravidade de Doença , Vitiligo/sangue , Adulto Jovem , beta-Defensinas/sangueRESUMO
Immunologic and genetic factors are involved in HIV-1/AIDS pathogenesis. Defensins are key molecules in innate immunity that participate in the control and/or development of infection and disease. Using PCR-RFLPs, we determined the association between HIV-1/AIDS and human ß-defensin 1 (DEFB1) 5'UTR -52 G/A (rs1799946), -44 C/G (rs1800972), and -20 G/A (rs11362) polymorphisms in three groups of women from the state of Sinaloa, located in the Northwest region of Mexico: i) healthy blood donors; ii) sex-workers; and iii) HIV-1 patients. The -52GG genotype was more frequent in blood donors than in patients (p= 0.023; Odds Ratio, OR= 0.49; 95% CI= 0.25-0.95), whereas the - 52GA genotype was significantly higher in patients (p= 0.013; OR= 2.03; 95% CI= 1.11-3.79, statistical power SP= 98.8%), as well as the frequencies of -20A allele (p= 0.017; OR= 1.60; 95% CI= 1.06-2.40), -20AA genotype (p= 0.047; OR = 2.02; 95% CI= 0.93-4.33) and the ACA haplotype with respect to healthy blood donors (p= 0.000012; OR= 5.82; 95% CI= 2.33-16.43, SP= 99.89%) and sex-workers (p= 0.019; OR= 2.18; 95% CI= 1.07-4.46). Conversely, the ACG haplotype was higher in healthy blood donors than in patients (p= 0.009; OR= 0.55; 95% CI= 0.34-0.89). In addition, the -44CC genotype was associated with a low plasma viral load (p= 0.015), whereas AGA, AGG and GGA haplotypes were more prevalent in individuals with high CD4 counts (p= 0.004, 0.046, and 0.029, respectively). These findings associate DEFB1 5'UTR polymorphisms with HIV-1/AIDS in Mexican women for the first time.
Assuntos
Regiões 5' não Traduzidas , Predisposição Genética para Doença , Infecções por HIV/epidemiologia , Infecções por HIV/genética , HIV-1/isolamento & purificação , Polimorfismo Genético , beta-Defensinas/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , México , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Medição de Risco , Adulto JovemRESUMO
Polymorphisms in the CAMP gene (cathelicidin) have not been tested in tuberculosis susceptibility. We tested polymorphisms rs9844812 (HIF-1α::ARNT binding site) and rs56122065 (CAMP) plus rs1800972 (DEFB1). SNP rs1800972 was associated with extrapulmonary tuberculosis (EPTB) in a codominant model (genotype CG, P = 0.037, OR 4.82; 95% CI: 0.92-47.42; statistical power, 82%), but not PTB (P = 0.101) in a Mexican population.
Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Predisposição Genética para Doença , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Polimorfismo Genético , Tuberculose/genética , Regiões 5' não Traduzidas , Alelos , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/química , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Sequência de Bases , Sítios de Ligação , Estudos de Casos e Controles , Éxons , Frequência do Gene , Genótipo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Dados de Sequência Molecular , Motivos de Nucleotídeos , Polimorfismo de Nucleotídeo Único , Matrizes de Pontuação de Posição Específica , Regiões Promotoras Genéticas , Ligação Proteica , Tuberculose/metabolismo , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/metabolismo , beta-Defensinas/genética , CatelicidinasRESUMO
Upon oxygen shift-down, Mycobacterium tuberculosis complex bacteria can induce a genetic program characterized by halted duplication, which is called Non-replicating persistence (NRP). During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions. It remains unclear whether expression of NRP genes occurs within the tissue of Mycobacterium bovis naturally infected cattle. In order to start dissecting this question, total RNA from bovine lymph node tissues of sacrificed tuberculin reacting animals was isolated and transcription of genes required for in vivo duplication (esxB and fbpB) and in vitro NRP (hspX, pfkB, and mb2660c) were analyzed by RT-PCR approaches. Detection of transcripts was positive in bovine tissue samples for genes hspX, pfkB, and mb2660c in 84, 32, and 21%, respectively. NRP genes were upregulated even in animals with a negative IFN-γ in vitro test, and the expression of NRP genes occurred more often than expression of the esxB gene.
Assuntos
Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Linfonodos/microbiologia , Mycobacterium bovis/crescimento & desenvolvimento , Regulação para Cima , Animais , Proteínas de Bactérias/genética , Bovinos , Interferon gama/biossíntese , Testes de Liberação de Interferon-gama , Mycobacterium bovis/genética , Mycobacterium bovis/metabolismo , Mycobacterium bovis/patogenicidade , Regulon , Testes Cutâneos , Teste Tuberculínico , Tuberculose Bovina/microbiologiaRESUMO
Polymerase chain reaction-restriction fragment length polymorphism assays for two single nucleotide polymorphisms in the human beta-defensin 1 gene have been validated with real-time PCR in 101 healthy individuals from western Mexico. Allele frequencies were 52.5% (692-A) and 98.5% (1836-A). These assays can be confidently used as a cheaper alternative genotyping method for these sites.