Association Analysis Suggests SOD2 as a Newly Identified Candidate Gene Associated With Leprosy Susceptibility.

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.

NOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in Brazilians.

Leprosy is a complex disease with phenotypes strongly influenced by genetic variation. A Chinese genome-wide association study (GWAS) depicted novel genes and pathways associated with leprosy susceptibility, only partially replicated by independent studies in different ethnicities. Here, we describe the results of a validation and replication study of the Chinese GWAS in Brazilians, using a stepwise strategy that involved two family-based and three independent case-control samples, resulting in 3,614 individuals enrolled. First, we genotyped a family-based sample for 36 tag single-nucleotide polymorphisms (SNPs) of five genes located in four different candidate loci: CCDC122-LACC1, NOD2, TNFSF15 and RIPK2. Association between leprosy and tag SNPs at NOD2 (rs8057431) and CCDC122-LACC1 (rs4942254) was then replicated in three additional, independent samples (combined OR(AA) = 0.49, P = 1.39e-06; OR(CC) = 0.72, P = 0.003, respectively). These results clearly implicate the NOD2 pathway in the regulation of leprosy susceptibility across diverse populations.

Complex segregation analysis of facial melasma in Brazil: evidence for a genetic susceptibility with a dominant pattern of segregation.

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.

Ceratopigmentação (tatuagem corneana): utilização de técnicas combinadas para melhora estética em olhos de pacientes com opacidades corneanas / Keratopigmentation (corneal tattooing): use of combined techniques for aesthetic improvement in eyes of patients with corneal opacities

RESUMO Objetivo: Relatar, por meio de uma série de casos, a percepção de pacientes com opacidade corneana sobre a eficácia da tatuagem na melhoria estética de seus olhos, utilizando a combinação de duas técnicas. Métodos: Oito pacientes responderam a um inquérito sobre sua satisfação estética com o procedimento, o desconforto pós-operatório e o impacto social observado após a cirurgia. Resultados: Todos os pacientes consideraram-se muito satisfeitos com os resultados. Em relação ao grau de desconforto no pós-operatório, 75% disseram ter tido pouco desconforto, e 25% relataram desconforto moderado. Todos os pacientes relataram melhora significativa no bem-estar social e pessoal. Da mesma forma, todos os pacientes disseram que repetiriam o procedimento. Conclusão: A tatuagem corneana surge como um método alternativo às lentes de contato e às próteses oculares em pacientes cegos com leucomas, trazendo resultados estéticos satisfatórios, duradouros e que podem promover impactos sociais na vida desses pacientes.

ABSTRACT Objective: To report, through a case series, the perception of patients about the effectiveness of corneal tattooing in the cosmetic improvement of their eyes with leukomas, using a combination of two techniques. Methods: Eight patients answered a survey regarding their cosmetic appearance satisfaction regarding the procedure, postoperative discomfort, and social impact observed after surgery. Results: All patients considered themselves very satisfied with the cosmetic results. Regarding the degree of postoperative discomfort, 75% said they had little discomfort, while 25% reported moderate discomfort. All patients reported significant improvement in social and personal well-being. Likewise, all patients said they would repeat the procedure. Conclusion: Corneal tattooing appears as an alternative method to contact lenses and ocular prostheses in impaired eyes with leukomas, bringing satisfactory and long-lasting cosmetic improvement that can promote social impacts for these patients.

Genetics of leprosy: Expected-and unexpected-developments and perspectives.

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 HLA and non-HLA 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 disease. 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; thus, strategies can be developed to study the functional impact of these variants in the context of infection, hopefully leading to the development of new targets for leprosy treatment and prevention.

Genetics of leprosy: expected and unexpected developments and perspectives.

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.