Association between macrophage migration inhibitory factor-173G/C polymorphism and psoriasis risk: A meta-analysis.

Background The association between macrophage migration inhibitory factor (MIF)-173G/C polymorphism and psoriasis risk has been reported in several studies with inconsistent conclusions. Aims This study aims to obtain a more convincing estimate of the relationship between the MIF-173G/C polymorphism and psoriasis risk. Methods Web of Science, EMBASE, PubMed, Wan Fang Database and Chinese National Knowledge Infrastructure (CNKI) were searched up to September 2021 and eligible studies were collected. The pooled odds ratios with 95% confidence intervals were calculated to estimate the effects of MIF-173G/C polymorphism on psoriasis risk under different genetic models. All analyses were conducted using the STATA12.0 software. Results A total of 1101 psoriasis cases and 1320 healthy controls from 6 relevant studies were included in this meta-analysis. Pooled analysis suggested that MIF-173G/C polymorphism was associated with increased psoriasis risk under the allelic model (C vs. G: odds ratio = 1.30, 95% confidence interval = 1.04-1.63, P = 0.020), heterozygous model (GC vs. GG: odds ratio = 1.53, 95% confidence interval = 1.05-2.22, P = 0.027) and dominant model (CC + GC vs. GG: odds ratio = 1.51, 95% confidence interval = 1.05-2.18, P = 0.027). Limitation Very few studies on the MIF-173G/C polymorphism in psoriasis have been reported till now, thus the number of studies included in the present meta-analysis was relatively small. Due to the number of studies being relatively small and the lack of raw data, stratified analysis by ethnicity or type of psoriasis was not carried out. Conclusion This meta-analysis demonstrated that MIF-173G/C polymorphism might be related to psoriasis risk. Carriers of the C allele and the GC genotype might have higher odds to present with psoriasis.

Cytokine gene polymorphisms in type I and type II reactions in Hansen's disease.

INTRODUCTION: Leprosy or Hansen's disease is a chronic debilitating disease caused by Mycobacterium leprae. Host genetics are believed to strongly influence the course of the disease. It is known that cytokines play an important role in leprosy and cytokine gene polymorphisms probably influence the course of the disease. METHODS: In the present study, we evaluated 70 patients with leprosy and 243 controls. DNA was extracted from the peripheral blood and genotyping was done for the following polymorphisms: IL-1 RA intron 2, IL-1ß-511 C/T and TNF-α A/G. RESULTS: A strong association of TNF-α-308 G/A polymorphism with Hansen's disease with both genotypes and alleles was found. However, no correlation was identified between the other two polymorphisms and Hansen's disease. A strong association between the IL-1ß gene polymorphisms and the type of reactions seen in leprosy was found. In contrast, the other two polymorphisms did not show any such association. LIMITATIONS: Genetic polymorphisms are association studies. They are not a direct reflection of the transcriptome or proteome and this is a major limitation of this study. CONCLUSION: In conclusion, cytokine gene polymorphisms appear to influence the susceptibility and course of Hansen's disease. An evaluation of the cytokine levels in the skin during lepra reactions would confirm this observation. Possibly, in future, this would be a guide to therapeutic decisions in cases of lepra reactions.

Distribution of killer immunoglobulin-like receptor genes in HIV infected long-term non-progressors from Mumbai, India.

BACKGROUND: Few reports suggest the association of killer immunoglobulin-like receptors of natural killer cells with human immunodeficiency virus infection. India with world's third largest population of human immunodeficiency virus / acquired immunodeficiency syndrome, offers scope to study such association. OBJECTIVE: Current study (2010-2015) was designed to evaluate if killer immunoglobulin-like receptors gene polymorphisms are associated with HIV infection outcomes specifically, with long term non progressors. METHODS: Killer immunoglobulin-like receptors genotyping was done using polymerase chain reaction - sequence-specific primer method. Viral load was measured by Cobas Taqman HIV-1 test. Estimation of CD4 counts was done using BD FACS CD4 count reagent. RESULTS: The activating gene frequencies identified were 3DS1 (53.8%), 2DS3 (69.2%), 2DS4 (76.9%), 2DS5 (69.2%), 2DS1 (76.9%) and 2DS2 (92.3%). The inhibitory gene frequencies were 2DL2 (92.3%), 2DL5 (76.9%), 2DL3 (69.5%), 3DL1 (84.6%), 3DL2 (92.3%) and 2DL1 (100%). The results highlight high frequency of 3DS1/3DL1 heterozygote and killer immunoglobulin-like receptor 2DS1, among these long term non progressors indicating their possible association with slow progression. Genotype analysis shows total 13 genotypes, of which 8 genotypes were identified for the first time from India. Two genotypes were unique/novel, which were unreported. All genotypes observed in this study were considered to be Bx genotype (100 %). LIMITATIONS: A small sample size (n=13, due to a rare cohort) and the absence of control group were the limitations of this study. CONCLUSIONS: The present study highlights the distribution of killer immunoglobulin-like receptor genes in a very rare group of human immunodeficiency virus -1 infected individuals - long term non progressors. All the long term non progressors tested show the presence of Bx haplotype and each long term non progressors has a different killer immunoglobulin-like receptor genotype.

Study of the relation between two common cyclooxygenase 2 gene polymorphisms with risk of developing and subtypes of vitiligo in Egyptian patients.

BACKGROUND/PURPOSE: Genetic factors play an important role in the pathogenesis of vitiligo. Cyclooxygenase 2 (COX2) gene induced by ultraviolet radiation controls the synthesis of prostaglandins, which are are found to be beneficial in treating vitiligo. COX2 gene polymorphism has been previously evaluated in Chinese population. We aimed to study the relation between two common COX2 gene polymorphisms with vitiligo and its subtypes amongEgyptian patients. PATIENTS AND METHODS: This study included 200 participants (100 vitiligo patients and 100 healthy controls). COX2-765G/C and -1195A/G gene polymorphism was studied by restriction fragment length polymorphism polymerase chain reaction analysis and the results were compared between the two groups and among different subtypes of vitiligo. RESULTS: Frequency of COX2-1195 AA, AG, GG genotypes showed no significant association among patients with vitiligo (P = 0.626, 0.321, 0.08, respectively); those with generalized vitiligo (P = 0.739, 0.291, 0.101, respectively) and those with segmental vitiligo (P = 0.410, 1.00, 0.676, respectively) compared to the control group. Regarding COX2-765G/C genotypes, GG genotype was more frequent among patients with vitiligo [84 (84%)] compared to controls [63 (63%)] (P = 0.001). GC genotype was significantly less frequent [15 (15%)] among patients compared to controls [32 (32%)] (P = 0.005). Generalized and segmental types of vitiligo also showed no significant difference in the frequency of COX2-765G/C genotypes compared with controls. LIMITATIONS: Being a pilot study, a relatively small number of participants were included. CONCLUSION: COX2-1195A/G gene polymorphism is not associated with the risk of developing vitiligo or with vitiligo subtypes. COX2-765 GG genotype is associated with vitiligo, especially of the generalized type.

Polymorphism of glutathione S-transferase M1 and T1 genes and susceptibility to psoriasis disease: A study from North India.

BACKGROUND: Increased oxidative stress and resulting inflammation has been emphasized as a factor in the pathogenesis of many diseases including psoriasis. Glutathione S-transferases (GSTs) protect against oxidative stress, inflammation, and genotoxicity. Polymorphisms in the GST genes may lead to an imbalance in pro- and antioxidant systems resulting in the increased production of reactive oxygen species that could influence the pathogenesis of psoriasis. AIM: The aim of this study was to investigate the association between GSTs (GSTM1 and GSTT1) gene polymorphism in patients with chronic plaque psoriasis as a factor in the susceptibility and development of psoriasis. MATERIALS AND METHODS: We assessed 128 patients with psoriasis and 250 age- and sex-matched healthy controls. Genomic DNA was extracted from peripheral blood by the phenol chloroform method. The null GSTT1 and GSTM1 genotypes were identified by multiplex polymerase chain reaction (PCR) method. RESULTS: The null genotype of GSTM1 and GSTT1 was seen in 45.3% and 40.6% in psoriasis patients whereas in the controls it was 34.4% and 20.0%, respectively. A significant association was seen between the null alleles of the GSTT1 (OR = 2.74) and GSTM1 (OR = 1.58) alone or in combination with tobacco use (P < 0.001) and psoriasis risk. The presence of both null genotypes of GSTM1 and GSTT1 further increased the risk of psoriasis (OR = 3.52) when compared with the positive genotypes of GSTM1 and GSTT1. LIMITATIONS: A major limitation of this study was the small sample size. A large epidemiological study is necessary to confirm these findings. CONCLUSIONS: The null genotype of GSTT1 is a strong predisposing factor for psoriasis in North India.

Polymorphisms in the TGFB1 and IL2RA genes are associated with clinical forms of leprosy in Brazilian population

BACKGROUND Leprosy is a chronic infectious disease caused by Mycobacterium leprae, and compromises the skin and peripheral nerves. This disease has been classified as multibacillary (MB) or paucibacillary (PB) depending on the host immune response. Genetic epidemiology studies in leprosy have shown the influence of human genetic components on the disease outcomes. OBJECTIVES We conducted an association study for IL2RA and TGFB1 genes with clinical forms of leprosy based on two case-control samples. These genes encode important molecules for the immunosuppressive activity of Treg cells and present differential expressions according to the clinical forms of leprosy. Furthermore, IL2RA is a positional candidate gene because it is located near the 10p13 chromosome region, presenting a linkage peak for PB leprosy. METHODS A total of 885 leprosy cases were included in the study; 406 cases from Rondonópolis County (start population), a hyperendemic region for leprosy in Brazil, and 479 cases from São Paulo state (replication population), which has lower epidemiological indexes for the disease. We tested 11 polymorphisms in the IL2RA gene and the missense variant rs1800470 in the TGFB1 gene. FINDINGS The AA genotype of rs2386841 in IL2RA was associated with the PB form in the start population. The AA genotype of rs1800470 in TGFB1 was associated with the MB form in the start population, and this association was confirmed for the replication population. MAIN CONCLUSIONS We demonstrated, for the first time, an association data with the PB form for a gene located on chromosome 10. In addition, we reported the association of TGFB1 gene with the MB form. Our results place these genes as candidates for validation and replication studies in leprosy polarisation.

Asociación de los polimorfismos T352C y A16974C con la lepra lepromatosa en pacientes cubanos / Association of T352C and A16974C polymorphisms with lepromatose leprosy in cuban patients

Introducción: La Lepra es una enfermedad infecciosa causada por el Mycobacterium leprae. Los patrones dermatoglíficos de pacientes cubanos con lepra lepromatosa mostraron indicios probatorios de que existe predisposición genética para el desarrollo de esta enfermedad, que sugiere la búsqueda de la asociación con polimorfismos moleculares, de mayor precisión. Entre estos, unos de los más estudiados son el T352C del gen del receptor de la vitamina D y el A16974C del gen IL12p40, cuya utilidad relativa depende de la población. Objetivo: Determinar si existe asociación entre la presencia de los polimorfismos T352C y A16974C con la lepra lepromatosa en pacientes cubanos. Material y Métodos: Se realizó un estudio observacional, analítico, de tipo caso-control de asociación genética donde se estudiaron pacientes con lepra lepromatosa y controles. Fueron identificados los genotipos relacionados con los polimorfismos T352C y A16974C en cada grupo. La prueba Chi-cuadrado de Pearson fue utilizada para determinar si los controles se hallaban en equilibrio de Hardy Weinberg, así como si existía relación entre los polimorfismos y la presencia de la enfermedad. Resultados: Los pacientes estudiados fueron 32 para el polimorfismo T352C y 44 para el A16974C. Los controles fueron 64 y 44, respectivamente; estos se hallaron en equilibrio Hardy-Weinberg. No se detectó asociaciónentre los polimorfismos A16974C y T352C con la lepra lepromatosa. Conclusiones: Los polimorfismos T352C y A16974C no son útiles como factor de riesgo predisponente en el grupo de pacientes cubanos con lepra lepromatosa estudiados(AU)

Introduction: Leprosy is an infectious disease caused by Mycobacterium leprae. Dermatoglyphic patterns of Cuban patients with lepromatose leprosy showed evidential signs of the existence of genetic predisposition to the development of this disease, which suggests a search for the association with molecular polymorphisms of higher degree of accuracy. Among them, some of the most studied are the T352C vitamin D receptor gene and the A16974Cof the IL12p40 gene, which relative usefulness depends on the population. Objective: To determine whether there is an association between the T352Cand A16974C polymorphisms with lepromatose leprosy in Cuban patients. Material and methods: An observational analytical case-control type genetic association study was conducted where patients with lepromatose leprosy and controls were studied. Genotypes related to T352Cand A16974C polymorphisms were identified in each group. Pearson´s chi square test was used to determine whether the controls were in Hardy-Weinberg equilibrium, and also whether there was a relation between polymorphisms and the presence of diseases. Results: There were 32 patients under study for T352C polymorphism, and 42 for A16974C. The controls were 64 and 44, respectively; and these were in Hardy-Weinberg equilibrium. No association between T352Cand A16974C polymorphisms with lepromatose leprosy was detected. Conclusions: T352Cand A16974C polymorphisms are not useful as a predisposing risk factor in the group of Cuban patients with lepromatose leprosy studied(AU)

Association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism and susceptibility to vitiligo: Systematic review and meta-analysis.

BACKGROUND: Protein tyrosine phosphatase, non-receptor type 22 gene, which translates to lymphoid tyrosine phosphatase, is considered to be a susceptibility gene marker associated with several autoimmune diseases. Several studies have demonstrated the association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism with vitiligo. However, these studies showed conflicting results. Meta-analysis of the same was conducted earlier that included fewer number of publications in their study. AIM: We performed a meta-analysis of a total of seven studies consisting of 2094 cases and 3613 controls to evaluate the possible association of protein tyrosine phosphatase, non-receptor type 22 +1858C>T polymorphism with vitiligo susceptibility. METHODS: We conducted a literature search in PubMed, Google Scholar and Dogpile for all published paper on protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism and vitiligo risk till June 2016. Data analysis was performed by RevMan 5.3 and comprehensive meta-analysis v3.0 software. RESULTS: Meta-analysis showed an overall significant association of protein tyrosine phosphatase, non- receptor type 22 +1858C→T polymorphism with vitiligo in all models (allelic model [T vs. C]: odds ratio = 1.50, 95% confidence interval [1.32-1.71], P< 0.001; dominant model [TT + CT vs. CC]: odds ratio = 1.61, 95% confidence interval [1.16-2.24], P = 0.004; recessive model [TT vs. CT + CC]: odds ratio = 4.82, 95% confidence interval [1.11-20.92], P = 0.04; homozygous model [TT vs. CC]: odds ratio = 5.34, 95% confidence interval [1.23-23.24], P = 0.03; co-dominant model [CT vs. CC]: odds ratio = 1.52, 95% confidence interval [1.09-2.13], P = 0.01). No publication bias was detected in the funnel plot study. LIMITATIONS: Limited ethnic-based studies, unable to satisfy data by gender or vitiligo-type are some limitations of the present meta-analysis. CONCLUSION: Stratifying data by ethnicity showed an association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T with vitiligo in European population (odds ratio = 1.53, 95% confidence interval [1.34-1.75], P< 0.001) but not in Asian population (odds ratio = 0.59, 95% confidence interval [0.26-1.32], P = 0.2). In conclusion, protein tyrosine phosphatase, non-receptor type 22 +1858 T allele predisposes European individuals to vitiligo.

Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample

Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.

Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample.

Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.

Conhecimento e prática dos enfermeiros sobre hanseníase: ações de controle e eliminação / Conocimiento y práctica de enfermeros acerca de hanseniasis: acciones de control y eliminación / Knowledge and practice of the nurse about leprosy: actions of control and elimination

RESUMO Objetivo: avaliar o conhecimento e a prática de enfermeiros da atenção primária de saúde quanto às ações de controle e eliminação da hanseníase. Método: estudo avaliativo, com abordagem qualitativa, utilizando o Discurso do Sujeito Coletivo, cujos dados foram obtidos por meio de entrevista semiestruturada, realizada com 16 enfermeiros. Resultados: os dados coletados revelaram que os profissionais de saúde possuem conhecimento suficiente sobre a Política Nacional de Controle e Eliminação da Hanseníase (PNCEH) e que as principais ações preconizadas foram executadas, porém, a notificação de casos suspeitos ou confirmados e a reinserção social do doente não foram citadas. Conclusão: manter os doentes em tratamento, sobrecarga de trabalho, falta de interdisciplinaridade e tratamento realizado em outros locais fora da comunidade foram dificuldades relatadas pelos profissionais. Os enfermeiros conhecem as ações direcionadas à assistência ao hanseniano, entretanto, o estudo aponta para a necessidade de uma prática mais alinhada ao que preconiza a PNECH. .

RESUMEN Objetivo: evaluar el conocimiento y la práctica de los enfermeros que trabajan en la atención primaria de salud como las acciones de control y eliminación de la hanseniasis. Método: es un estudio evaluativo con enfoque cualitativo, utilizando el Discurso del Sujeto Colectivo, cuyos datos fueron recolectados a través de entrevistas semi-estructuradas con 16 enfermeros. Resultados: los datos obtenidos revelaron que los profesionales de la salud tienen el conocimiento suficiente sobre la Política Nacional de Control y Erradicación de la Hanseniasis (PNCEH) y que las principales acciones recomendadas se han implementado, pero la notificación de los casos sospechosos o confirmados y reinserción social del paciente no fue mencionado. Conclusión: mantener a los pacientes en tratamiento, exceso de trabajo, falta de interdisciplinariedad y tratamiento realizado en otros lugares fuera de la comunidad fueron problemas reportados por el personal de salud. Los enfermeros conocen las acciones destinadas a ayudar a los pacientes con hanseniasis, sin embargo, el estudio apunta la necesidad de una practica más direccionado a lo que defiende la PNECH. .

ABSTRACT Objective: to assess the knowledge and practice of primary health care nurses about control and elimination actions of leprosy. Method: evaluation study with qualitative approach, using the Discourse of the Collective Subject, data were collected through semi-structured interviews conducted with 16 nurses. Results: the data collected revealed that health professionals have suffi cient knowledge about the National Policy on Control and Elimination of Leprosy (NPCEL) and that the main actions preconized were applied, however, notifi cation of suspected or confi rmed cases and social reintegration of the patient were not mentioned. Conclusion: keeping patients in treatment, overload of work, lack of interdisciplinarity and treatment performed at other locations outside of the community were diffi culties reported by professionals. Nurses know the actions addressed at assistance of leprosy patients, however, the study points to the need for a practice which is more aligned to what advocates NPCEL. .

LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations.

In recent years, genome wide association studies have discovered a large number of gene loci that play a functional role in innate and adaptive immune pathways associated with leprosy susceptibility. The immunological control of intracellular bacteria M. leprae is modulated by NOD2-mediated signaling of Th1 responses. In this study, we investigated 211 clinically classified leprosy patients and 230 ethnically matched controls in Indian population by genotyping four variants in NOD2 (rs9302752A/G), LRRK2 (rs1873613A/G), RIPK2 (rs40457A/G and rs42490G/A). The LRRK2 locus is associated with leprosy outcome. The LRRK2 rs1873613A minor allele and respective rs1873613AA genotypes were significantly associated with an increased risk whereas the LRRK2 rs1873613G major allele and rs1873613GG genotypes confer protection in paucibacillary and leprosy patients. The reconstructed GA haplotypes from RIPK2 rs40457A/G and rs42490G/A variants was observed to contribute towards increased risk whereas haplotypes AA was observed to confer protective role. Our results indicate that a possible shared mechanisms underlying the development of these two clinical forms of the disease as hypothesized. Our findings confirm and validates the role of gene variants involved in NOD2-mediated signalling pathways that play a role in immunological control of intracellular bacteria M. leprae.

Epidemiologia genética em hanseníase: estudo de associação da região genômica candidata 6p21 e do gene TLR1 / Genetic epidemiology of leprosy: association study of the genomic region 6p21 canditate and TLR1 gene

A hanseníase é uma doença infecciosa crônica, que acomete pele e sistema nervoso periférico e tem como agente etiológico o Mycobacterium leprae, um patógeno exclusivamente intracelular, que tem predileção por macrófagos e pelas células de Schwann. É um traço complexo e fatores genéticos do hospedeiro têm sido repetidamente implicados com o risco para a doença. A região cromossômica 6p21 vem sendo sistematicamente envolvida com a hanseníase, não só pelos genes do HLA de classe II, como também pelos estudos envolvendo marcadores em genes como o TNF e a LTA. O gene TLR1 também é um importante candidato e polimorfismos deste já têm sido associados com hanseníase per se e com reação hansênica. O objetivo desta pesquisa foi conduzir estudo de associação de base populacional do tipo caso-controle em hanseníase testando marcadores do tipo tag SNPs em genes candidatos da região cromossômica candidata 6p21 e do gene TLR1. Oitenta e nove marcadores do tipo tag SNPs, localizados em trinta e seis genes foram genotipados. O presente trabalho envolveu 1718 indivíduos, 981 casos e 737 controles, provenientes de dois estados brasileiros: Mato Grosso e São Paulo. As genotipagens da população de Rondonópolis, MT foram realizadas em plataforma de médio rendimento (VeraCode GoldenGate Genotyping Assay – Illumina) e as genotipagens da população de São Paulo foram feitas usando discriminação alélica baseada na tecnologia TaqMan (Applied Biosystems). Para as análises estatísticas foi empregado modelo de regressão logística, com correção para as co-variáveis etnia e sexo, usando o software R, para Windows. Treze genes localizados na região 6p21 tiveram marcadores associados com hanseníase per se. O alelo S do polimorfismo N248S do gene TLR1 também foi associado com susceptibilidade para hanseníase per se...

Leprosy is an chronic infectious disease that attacks skin and peripheral nervous system. The causative agent is Mycobacterium leprae, an obligate intracellular pathogen that infects macrophage and Schwann cells. It is a complex trait and host genetic factors have been extensively implicated in leprosy susceptibility. The chromosomal region 6p21 has been involved with leprosy susceptibility due to HLA class II, and TNF and LTA genes, as well. The TLR1 gene is also an important candidate gene and polymorphisms at this locus have been associated to leprosy per se and leprosy reactions. This research is a population-based association study in leprosy which tested tag SNPs located at candidate genes in chromosomal region 6p21 and in TLR1 gene. Eighty-nine markers distributed in thirty-six genes were genotyped. The present work enrolled 1,718 individuals, 981 cases and 737 controls from Mato Grosso and São Paulo States, Brazil. The genotypes for Rondonópolis population were obtained using by medium-scale genotyping platform (VeraCode GoldenGate Genotyping Assay – Illumina), while to São Paulo samples the genotyping were done by allelic discrimination based on TaqMan technology (Applied Biosystems). Statistical analysis were performed by logistic regression models adjusted for the covariates sex and ethnicity, using R software. Thirteen genes located at 6p21 region presented markers associated to leprosy per se. The S allele for N248S polymorphism at TLR1gene was also associated to leprosy susceptibility...

Interleukin 4-590T/C polymorphism and susceptibility to leprosy.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Cell-mediated (Th1) immune response and humoral (Th2) immune response play different roles in leprosy infection. Interleukin 4 (IL-4) is a typical Th2 cytokine. It is a critical mediator of the Th1/Th2 balance. OBJECTIVE: The objective of this study is to investigate the association between IL-4 gene -590T/C polymorphism and the susceptibility to leprosy in a Chinese population. METHODS: The IL-4 variant -590T/C was detected by polymerase chain reaction-restriction fragment length polymorphism in 432 leprosy cases and 465 age-matched healthy controls. Data were analyzed using the chi-square test. RESULTS: Frequencies of the IL-4-590TC and CC genotypes and the -590C allele were significantly lower in patients with leprosy than in healthy controls (odds ratio [OR]=0.74, 95% confidence interval [CI] 0.55-0.99, p=0.044; OR=0.46, 95% CI 0.25-0.84, p=0.010; and OR=0.68, 95% CI 0.54-0.86, p=0.001, respectively). CONCLUSIONS: Our data suggest that the -590T/C polymorphism of the IL-4 gene is associated with decreased susceptibility of leprosy.

[NRAMP1 gene polymorphisms in individuals with leprosy reactions attended at two reference centers in Recife, northeastern Brazil]. / Polimorfismos do gene NRAMP1 em indivíduos com reações hansênicas, atendidos em dois Centros de Referência no Recife, nordeste do Brasil.

INTRODUCTION: To investigate susceptibility to leprosy reactions, three polymorphisms of the natural resistance-associated macrophage protein (NRAMP1) gene were determined in 201 individuals who were attended at two reference centers in Recife, between 2007 and 2008. Of these, 100 were paucibacillary and 101 were multibacillary. METHODS: The 274C/T, D543N and 1729+55del4 polymorphisms of the NRAMP1 gene were determined using the technique of restriction fragment polymorphism on DNA extracted from peripheral blood. Allelic and genotypic frequencies were estimated by direct counting. RESULTS: The predominant genotypes were: CC (51.8%) for 274C/T; GG (86.6%) for D543N; and +-TGTG (59.9%) for 1729+55del4. The mutant genotype 274 TT predominated in negativity of the reverse reaction (p = 0.03) and in positivity of erythema nodosum leprosum (p = 0.04). CONCLUSIONS: Our results suggest that 274 C/T polymorphism of the NRAMP1 gene may aid in determining the susceptibility to type II reactions among leprosy patients.

Polimorfismos do gene NRAMP1 em indivíduos com reações hansênicas, atendidos em dois Centros de Referência no Recife, nordeste do Brasil / NRAMP1 gene polymorphisms in individuals with leprosy reactions attended at two reference centers in Recife, northeastern Brazil

INTRODUÇÃO: Para investigar susceptibilidade às reações hansênicas, três polimorfismos do gene natural resistance-associated macrophage protein (NRAMP1), foram determinados em 201 indivíduos, atendidos em dois centros de referência no Recife, entre 2007 e 2008, sendo 100 paucibacilares e 101 multibacilares. MÉTODOS: A determinação dos polimorfismos 274C/T, D543N e 1729+55del4 do gene NRAMP1 foi realizada utilizando a técnica do polimorfismo de fragmento de restrição em DNA extraído de sangue periférico e as estimativas das freqüências alélicas e genotípicas foram feitas por contagem direta. RESULTADOS: Os genótipos predominantes foram: CC (51,8 por cento) para 274C/T, GG (86,6 por cento) para D543N e +-TGTG (59,9 por cento) para 1729+55del4. O genótipo mutante 274 TT predominou na negatividade da reação reversa (p=0,03) e na positividade do eritema nodoso (p=0,04). CONCLUSÕES: Nossos resultados sugerem que o polimorfismo 274 C/T do gene NRAMP1 pode auxiliar na determinação da susceptibilidade à reação tipo II em indivíduos com hanseníase.

INTRODUCTION: To investigate susceptibility to leprosy reactions, three polymorphisms of the natural resistance-associated macrophage protein (NRAMP1) gene were determined in 201 individuals who were attended at two reference centers in Recife, between 2007 and 2008. Of these, 100 were paucibacillary and 101 were multibacillary. METHODS: The 274C/T, D543N and 1729+55del4 polymorphisms of the NRAMP1 gene were determined using the technique of restriction fragment polymorphism on DNA extracted from peripheral blood. Allelic and genotypic frequencies were estimated by direct counting. RESULTS: The predominant genotypes were: CC (51.8 percent) for 274C/T; GG (86.6 percent) for D543N; and +-TGTG (59.9 percent) for 1729+55del4. The mutant genotype 274 TT predominated in negativity of the reverse reaction (p = 0.03) and in positivity of erythema nodosum leprosum (p = 0.04). CONCLUSIONS: Our results suggest that 274 C/T polymorphism of the NRAMP1 gene may aid in determining the susceptibility to type II reactions among leprosy patients.

Population polymorphism of nuclear mitochondrial DNA insertions reveals widespread diploidy associated with loss of heterozygosity in Debaryomyces hansenii.

Debaryomyces hansenii, a yeast that participates in the elaboration of foodstuff, displays important genetic diversity. Our recent phylogenetic classification of this species led to the subdivision of the species into three distinct clades. D. hansenii harbors the highest number of nuclear mitochondrial DNA (NUMT) insertions known so far for hemiascomycetous yeasts. Here we assessed the intraspecific variability of the NUMTs in this species by testing their presence/absence first in 28 strains, with 21 loci previously detected in the completely sequenced strain CBS 767(T), and second in a larger panel of 77 strains, with 8 most informative loci. We were able for the first time to structure populations in D. hansenii, although we observed little NUMT insertion variability within the clades. We determined the chronology of the NUMT insertions, which turned out to correlate with the previously defined taxonomy and provided additional evidence that colonization of nuclear genomes by mitochondrial DNA is a dynamic process in yeast. In combination with flow cytometry experiments, the NUMT analysis revealed the existence of both haploid and diploid strains, the latter being heterozygous and resulting from at least four crosses among strains from the various clades. As in the diploid pathogen Candida albicans, to which D. hansenii is phylogenetically related, we observed a differential loss of heterozygosity in the diploid strains, which can explain some of the large genetic diversity found in D. hansenii over the years.

Use of short tandem repeat sequences to study Mycobacterium leprae in leprosy patients in Malawi and India.

BACKGROUND: Inadequate understanding of the transmission of Mycobacterium leprae makes it difficult to predict the impact of leprosy control interventions. Genotypic tests that allow tracking of individual bacterial strains would strengthen epidemiological studies and contribute to our understanding of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Genotyping assays based on variation in the copy number of short tandem repeat sequences were applied to biopsies collected in population-based epidemiological studies of leprosy in northern Malawi, and from members of multi-case households in Hyderabad, India. In the Malawi series, considerable genotypic variability was observed between patients, and also within patients, when isolates were collected at different times or from different tissues. Less within-patient variability was observed when isolates were collected from similar tissues at the same time. Less genotypic variability was noted amongst the closely related Indian patients than in the Malawi series. CONCLUSIONS/SIGNIFICANCE: Lineages of M. leprae undergo changes in their pattern of short tandem repeat sequences over time. Genetic divergence is particularly likely between bacilli inhabiting different (e.g., skin and nerve) tissues. Such variability makes short tandem repeat sequences unsuitable as a general tool for population-based strain typing of M. leprae, or for distinguishing relapse from reinfection. Careful use of these markers may provide insights into the development of disease within individuals and for tracking of short transmission chains.

Typing of Thai clinical isolates of Mycobacterium leprae and analysis of leprosy transmission by polymorphism of tandem repeats.

Mycobacterium leprae isolates from Thai leprosy patients were typed for strain differentiation and analysis of leprosy transmission using the six base tandem repeat, GACATC, in rpoT gene and TTC repeat as genetic markers. M. leprae DNA was isolated from skin biopsies of new untreated leprosy patients living in remote areas or in suburban regions of Thailand where leprosy is in low prevalence. In M. leprae strains of 100 patients, TTC alleles exhibited variations in length with 10 to 30, 33 and 35 repeats, the most common alleles being 15, 16, 17 and 19 repeats. All isolates contained three copies of the six base repeat in rpoT gene. Application of TTC repeats in tracking leprosy transmission in two families with multi-cases identified a single (but different) strain of M. leprae in each family.