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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 2 independent population samples. Family-based analysis revealed an association between leprosy and allele G of marker rs295340 (P = .042) and borderline evidence of an association between leprosy and alleles C and A of markers rs4880 (P = .077) and rs5746136 (P = .071), respectively. Findings were validated in an independent case-control sample for markers rs295340 (P = .049) and rs4880 (P = .038). These results suggest SOD2 as a newly identified gene conferring susceptibility to leprosy.

Made available in DSpace on 2018-12-11T17:22:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 Despite high prevalence, the etiopathology of melasma is not fully understood. Nevertheless, many factors have been associated with the disease, including: sun exposure, sex steroids hormones, drugs, stress, and pregnancy. The high occurrence within familiars (40–60%) suggests a genetic predisposition to the disease. This study explored, through complex segregation analysis (CSA), the inheritance model that best fit the family segregation pattern of facial melasma when accounting for the main epidemiological risk factors. We evaluated 686 subjects from 67 families, and 260 (38%) of them had facial melasma. The CSA model, adjusted for age, skin phototype, sex, sun exposure at work, hormonal oral contraceptive, and pregnancy, evidenced a genetic component that was best fitted to a dominant pattern of segregation. Melasma results from an interaction between exposure factors (e.g. pregnancy, hormones, and sun exposure) over genetically predisposed individuals. Departamento de Dermatologia e Radioterapia SN FMB-Unesp, Campus de Rubião Jr. Programa de Pós-Graduação em Ciências da Saúde Escola de Medicina Pontifícia Universidade Católica do Paraná Programa de Pós-Graduação em Odontologia Escola de Ciências da Vida Pontifícia Universidade Católica do Paraná Departamento de Dermatologia e Radioterapia SN FMB-Unesp, Campus de Rubião Jr.

A solid body of evidence produced over decades of intense research supports the hypothesis that leprosy phenotypes are largely dependent on the genetic characteristics of the host. The early evidence of a major gene effect controlling susceptibility to leprosy came from studies of familial aggregation, twins, and Complex Segregation Analysis. Later, linkage and association analysis, first applied to the investigation of candidate genes and chromosomal regions and more recently, to genome-wide scans, have revealed several leukocyte antigen complex and nonleukocyte antigen complex gene variants as risk factors for leprosy phenotypes such as disease per se, its clinical forms and leprosy reactions. In addition, powerful, hypothesis-free strategies such as Genome-Wide Association Studies have led to an exciting, unexpected development: Leprosy susceptibility genes seem to be shared with Crohn's and Parkinson's diseases. Today, a major challenge is to find the exact variants causing the biological effect underlying the genetic associations. New technologies, such as Next Generation Sequencing that allows, for the first time, the cost and time-effective sequencing of a complete human genome, hold the promise to reveal such variants. Strategies can be developed to study the functional effect of these variants in the context of infection, hopefully leading to the development of new targets for leprosy treatment and prevention.

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. INTRODUÇÃO: Durante a era pré-microbiológica, era comum a visão de que doenças, hoje sabidamente infecciosas, eram hereditárias. Com a descoberta dos microorganismos e seu papel na patogênese de diversas patologias, chegou-se a propor que a exposição ao patógeno era condição suficiente para explicar infecção. Hoje, está claro que infecção é o resultado de uma complexa interação entre patógeno e hospedeiro, dependendo portanto, em última análise, do make-up genético de ambos os organismos. A dermatologia oferece diversos exemplos de doenças infecciosas em diferentes graus de entendimento de suas bases moleculares. Nesta revisão, resumimos os principais avanços na direção da dissecção do componente genético controlando suscetibilidade do ser humano a doenças infecciosas de importância na dermatologia. Doenças amplamente estudadas, como a hanseníase e a leishmaniose, são discutidas sob o ponto de vista da genética tanto do hospedeiro quanto do patógeno. Outras, como micobacterioses raras, micoses e sífilis, são apresentadas como boas oportunidades para pesquisa na área de genética de infecção.

Aim The objective of this study was to evaluate the influence of HLA and MICA alleles in the development of leprosy and its clinical forms in a population with leprosy from the region of Santo Antonio do Prata – PA, Brazil. Methods Fifty-one families were genotyped for HLA and MICA genes by PCR-SSOP, LuminexO methodology (One Lambda) and Dynal AutoRELITM 48 Instrument (Invitrogen) Dynal-RELITM SSO HLA Typing. Statistical Analysis was based on the Transmission Disequilibrium Test (TDT) software FBAT 2.0.4. Results The alleles HLA-A∗03/11 (P=0.041), HLA-C∗04 (P=0.025), HLA-DRB1∗16 (P=0.048), DQB1∗05 (P=0.004) and MICA∗002 (P = 0.003) showed significant positive association with the occurrence of leprosy in this population, while the alleles HLA-C∗12 (P = 0.095), DRB1∗15/16 (P = 0.055), and MICA∗008 (P = 0.075) showed a tendency to positive association. Conclusions This study suggests that the alleles HLA-A∗03/∗11, HLA-C∗04, HLA-DRB1∗16, DQB1∗05 and MICA∗002 may be associated with susceptibility to leprosy in this population and HLA-C∗12, DRB1∗15/16 and MICA∗008 should be further investigated.