A Major Gene Controls Leprosy Susceptibility in a Hyperendemic Isolated Population from North of Brazil

Lazaro, F.; Werneck, Renata Iani; Mackert, Ciane C. O.; Cobat, Aurélie; Prevedello, Flávia Costa; Pimentel, Raphaela P.; Macedo, Geraldo Mariano Moraes de; Eleutário, Marco A. M.; Vilar, Guilherme; Abel, Laurent; Xavier, Marília Brasil; Alcaïs, Alexandre; Mira, Marcelo Távora

doi:10.1086/652007

Cited by 38 publications

(27 citation statements)

References 41 publications

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“…Isolation was compulsory until 1962; however, the population of the colony remains isolated today, probably due to the strong stigma associated with leprosy, a disease still highly prevalent within the community. Previous assessment indicated very homogenous environmental and socioeconomic variables and predominance of a mixed ethnic group, as reported elsewhere (Lázaro et al, 2010). Family recruitment was performed by a systematic approach intended to reduce ascertainment bias.…”

Section: Study Population and Enrollment Strategymentioning

confidence: 91%

“…In the first model, sporadic transmission (model I) includes only the nongenetic covariates with significant impact over disease susceptibility. Next, in addition to the significant covariates, the dependence on phenotypes of preceding relatives, which is parameterized in terms of familial correlations (model II), is included in the model, with the class D pattern of familial correlations (Lázaro et al, 2010). Four types of phenotypic familial correlation were considered: father-mother (FM), father-offspring (FO), mother-offspring (MO), and sib-sib (SS), with corresponding regression coefficients denoted as "ρ FM ", "ρ FO ", "ρ MO ", and "ρ SS ", respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Here we present the results of a Complex Segregation Analysis for caries performed in a sample of the Colony of Santo Antônio do Prata (the Prata Colony), a community geographically isolated in the Amazonian state of Pará, north of Brazil. The population of the Prata Colony is highly exposed to caries susceptibility factors and shares very homogenous non-genetic variables (Lázaro et al, 2010).…”

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A Major Gene Effect Controls Resistance to Caries

et al. 2011

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A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental. AbSTRACT Despite recent advances revealing genetic factors influencing caries susceptibility, questions regarding the model of inheritance involved are yet to be addressed. We conducted a Complex Segregation Analysis on decayed teeth in a sample of homogenous, isolated families recruited from the Brazilian Amazon. A dominant, major gene effect controlling resistance to phenotype was detected. The frequency of the resistance allele "A" was 0.63; mean numbers of decayed teeth were 1.53 and 9.53 for genotypes AA/AB and BB, respectively. These results represent a step toward a description of the exact nature of the genetic risk factors controlling human susceptibility to caries.

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Section: Study Population and Enrollment Strategymentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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A Major Gene Effect Controls Resistance to Caries

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“…4 Both diseases are chronic granulomatous infections caused by intracellular Gram-positive aerobic acid-fast bacilli that multiply slowly and have long incubation periods. According to Lázaro and others, 5 about 5% of the Mycobacterium lepraeinfected individuals in endemic areas are predisposed to leprosy. A similar figure holds for TB: more than 90% of the infected individuals will not develop the disease.…”

Section: Introductionmentioning

confidence: 98%

Leprosy and Tuberculosis Co-Infection: Clinical and Immunological Report of Two Cases and Review of the Literature

Trindade¹,

Miyamoto²,

Benard³

et al. 2013

The American Journal of Tropical Medicine and Hygiene

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Abstract. A review of the records of patients seen between 2004 and 2011 at the Dermatology Clinic of the Sã o Paulo University Medical School showed that only two leprosy patients had been co-infected with tuberculosis (TB). One patient showed a type 1 leprosy reaction during the first 3 months of treatment of pleural TB and in the other patient, pulmonary TB was diagnosed during the first 3 months of treatment of a type 1 leprosy reaction. Both patients showed normal cellular immune response tests, including those of the interferon-gamma (IFN-γ)/interleukin 12 (IL-12) axis. Although both mycobacterial infections are endemic in developing countries like Brazil, the co-infection has hardly been reported in the last decade. There is no suitable explanation for this observation. The reports on the interaction between the two mycobacteria are highly speculative: some studies suggest that leprosy, especially the anergic form, would predispose to TB, whereas other investigations suggested an antagonism between the two diseases.

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“…The application of this tool of analysis to different populations has shown that susceptibility to leprosy has a significant genetic component, probably with a major co-dominant or recessive gene controlling susceptibility to the disease. 8,9 Association and linkage analysis identified several genes and chromosomal regions involved in classical and non-classical immune response against M. leprae. 10 Of note, leprosy was the first infectious disease found to be associated with specific Human Leukocyte Antigen (HLA) variants.…”

Section: Host Genetics and Susceptibility To Leprosymentioning

confidence: 99%

Genetic risk factors for human susceptibility to infections of relevance in dermatology

Sardinha

Tarlé

Fava

et al. 2011

An. Bras. Dermatol.

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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. Keywords: Dermatology; Infection; Polymorphism, genetic Resumo: 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.

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A Major Gene Controls Leprosy Susceptibility in a Hyperendemic Isolated Population from North of Brazil

Abstract: A strong major gene effect in the isolated, hyperendemic Prata Colony indicates enrichment of genetic risk factors, suggesting a population particularly suitable for leprosy gene identification studies.

Cited by 38 publications

References 41 publications

A Major Gene Effect Controls Resistance to Caries

A Major Gene Effect Controls Resistance to Caries

Leprosy and Tuberculosis Co-Infection: Clinical and Immunological Report of Two Cases and Review of the Literature

Genetic risk factors for human susceptibility to infections of relevance in dermatology

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