Publications (4)12.74 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Genetic studies have identified several genes and genomic regions contributing to the control of host susceptibility to leprosy. Here, we test variants of the positional and functional candidate gene SOD2 for association with leprosy in two independent population samples. Family-based analysis revealed association between leprosy and allele G of marker rs295340 (P=0.042), and borderline evidence of association between leprosy and alleles C and A of markers rs4880 (P=0.077) and rs5746136 (P=0.071), respectively. Findings were validated in an independent case-control sample for markers rs295340 (P=0.049) and rs4880 (P=0.038). These results suggest SOD2 as a new leprosy susceptibility gene.
- [Show abstract] [Hide abstract] ABSTRACT: Leprosy is an infectious disease caused by Mycobacterium leprae. Tumor necrosis factor (TNF) plays a key role in the host response. Some association studies have implicated the single nucleotide polymorphism TNF -308G>A in leprosy susceptibility, but these results are still controversial. We first conducted 4 association studies (2639 individuals) that showed a protective effect of the -308A allele (odds ratio [OR] = 0.77; P = .005). Next, results of a meta-analysis reinforced this association after inclusion of our new data (OR = 0.74; P = .04). Furthermore, a subgroup analysis including only Brazilian studies suggested that the association is specific to this population (OR = 0.63; P = .005). Finally, functional analyses using whole blood cultures showed that patients carrying the -308A allele produced higher TNF levels after lipopolysaccharide (LPS) (6 hours) and M. leprae (3 hours) stimulation. These results reinforce the association between TNF and leprosy and suggest the -308A allele as a marker of disease resistance, especially among Brazilians.
- [Show abstract] [Hide abstract] ABSTRACT: Background: In the pre-microbiological era, it was widely accepted that diseases, today known to be infectious, were hereditary. With the discovery of microorganisms and their role in the pathogenesis of several diseases, it was suggested that exposure to the pathogen was enough to explain infection. Nowadays, it is clear that infection is the result of a complex interplay between pathogen and host, therefore dependant on the genetic make-up of the two organisms. Dermatology offers several examples of infectious diseases in different stages of understanding of their molecular basis. In this review, we summarize the main advances towards dissecting the genetic component controlling human susceptibility to infectious diseases of interest in dermatology. Widely investigated diseases such as leprosy and leishmaniasis are discussed from the genetic perspective of both host and pathogen. Others, such as rare mycobacterioses, fungal infections and syphilis, are presented as good opportunities for research in the field of genetics of infection.
- [Show abstract] [Hide abstract] ABSTRACT: Leprosy is a chronicle infectious disease that still affects approximately 215 000 individuals worldwide. Clinical and epidemiological observations suggest that only a small proportion of the population exposed to Mycobacterium leprae develop the disease. Today, it is known that mechanisms controlling susceptibility to leprosy phenotypes strongly depend on the genetic background of the host. This review summarizes the latest advances in the field, obtained from genetic epidemiology and functional studies. Copyrigth © Sociedad Iberoamericana de Información Científica (SIIC), 2011.