RESUMO
Several human genetic variants have been associated with susceptibility or resistance to leprosy. The aim of this study was to assess whether gene polymorphisms of -308 G/A TNF-alpha and -819 T/C IL-10 are associated with lepromatous leprosy in Mexican mestizos patients from northwest Mexico. We genotyped these polymorphisms by means of polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLPs) in 68 patients with lepromatous leprosy and 144 healthy Mexican Mestizos controls. We found that the -308G TNF-alpha allele was predominant in both cases (94.3%) and controls (92.3%) without statistical significance and the frequencies of -819C IL-10 allele were also similar for the cases (56.0%) and controls (59.0%). These negative findings suggest that other genes or polymorphisms may be important in the susceptibility to leprosy infection in the Mexican mestizos.
Assuntos
Interleucina-10/genética , Hanseníase Virchowiana/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Testes Genéticos , Humanos , Hanseníase Virchowiana/epidemiologia , Hanseníase Virchowiana/patologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Grupos Populacionais , Regiões Promotoras Genéticas , Adulto JovemRESUMO
UNLABELLED: Leprosy is an infectious disease caused by Mycobacterium leprae. The peptide human beta-defensin 1 is an antimicrobial effector of innate epithelial immunity. A study was done on the association of three single nucleotide polymorphisms (SNPs) in the beta-defensin 1 gene (DEFB1) - 668 C/G (-44 C/G or rs1800972; in 5' UTR), 692 A/G (-20 A/G or rs11362; in 5' UTR) and A1836G (rs1800971; in 3' UTR) - with leprosy susceptibility per se and clinical leprosy variants. The SNPs were genotyped by real-time polymerase chain reaction (rt-PCR) and PCR-restriction fragment length polymorphisms. Subjects were of Mexican mestizo ethnicity from Sinaloa state, México. Analysis was done on borderline leprosy, lepromatous leprosy (L-lep) and indeterminate leprosy subgroups compared with healthy controls. RESULTS: The genotypes associated with L-lep and no other leprosy subgroup after Bonferroni correction were those that contain 668C in a dominant model (OR=3.06, 95% CI 1.47-6.4, p=0.024). Estimated haplotype CGA is over-represented in L-lep (p=0.009; OR=2.25, 1.23-4.03). Five NF-kappaB1 putative binding sites (NPBSs) were identified with JASPAR software in non-coding strand spanning the 5' UTR and intron 1 of DEFB1, including one which is altered when SNP 668C is present. SNP 668C probably abrogates NF-kappaB-dependent DEFB1 upregulation leading to L-lep variant.
Assuntos
Predisposição Genética para Doença , Hanseníase Virchowiana/genética , Polimorfismo de Nucleotídeo Único , beta-Defensinas/genética , Sequência de Bases , Sítios de Ligação , Distribuição de Qui-Quadrado , Haplótipos , Humanos , Hanseníase Virchowiana/imunologia , Desequilíbrio de Ligação , México , Modelos Genéticos , Dados de Sequência Molecular , NF-kappa B/metabolismo , Polimorfismo de Fragmento de Restrição , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJETIVO: Determinar la relación del polimorfismo TaqI del gen del receptor de la vitamina D (RVD) con la lepra lepromatosa (LL) en individuos originarios de Sinaloa, México. MATERIAL Y MÉTODOS: Se amplificó un fragmento de 740 pb del gen RVD en muestras de ADN de 71 pacientes con LL y 144 controles en el Hospital General de Culiacán durante el periodo 2004-2007. El polimorfismo se identificó mediante la endonucleasa TaqI. RESULTADOS: Se observó un aumento de relevancia estadística del genotipo TT en pacientes con LL en comparación con los controles (p= 0.040; RM= 1.82). CONCLUSIÓN: Se demuestra un nexo entre el genotipo TT y la susceptibilidad a la LL.
OBJETIVE: To establish the association of the vitamin D receptor gene TaqI polymorphism with lepromatous leprosy (LL) in individuals from Sinaloa, Mexico. MATERIAL AND METHODS: A 740 bp fragment was amplified from the VDR gene in DNA samples of 71 patients with LL and 144 controls in the Hospital General de Culiacán during 2004-2007. Polymorphism was identified through TaqI endonuclease. RESULTS: A significant increase in the genotype TT of the VDR gene was observed in patients when compared to controls (p = 0.040; OR = 1.82). CONCLUSIONS: Our data support the association between the TT genotype and susceptibility to LL in this Mexican population.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Hanseníase Virchowiana/genética , Polimorfismo de Fragmento de Restrição , Receptores de Calcitriol/genética , Estudos de Casos e Controles , Éxons/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Hanseníase Virchowiana/epidemiologia , México/epidemiologia , Taq Polimerase , Adulto JovemRESUMO
OBJECTIVE: To establish the association of the vitamin D receptor gene TaqI polymorphism with lepromatous leprosy (LL) in individuals from Sinaloa, Mexico. MATERIAL AND METHODS: A 740 bp fragment was amplified from the VDR gene in DNA samples of 71 patients with LL and 144 controls in the Hospital General de Culiacán during 2004-2007. Polymorphism was identified through TaqI endonuclease. RESULTS: A significant increase in the genotype TT of the VDR gene was observed in patients when compared to controls (p = 0.040; OR = 1.82). CONCLUSIONS: Our data support the association between the TT genotype and susceptibility to LL in this Mexican population.