RESUMO
OBJECTIVE: To determine the occurrence and characteristics of the two types of lepra reactions in new leprosy cases at initial diagnosis. METHODS: The retrospective descriptive study was conducted at the Marie Adelaide Leprosy Centre, Karachi, and comprised all new leprosy cases registered from January 1, 2016, to June 30, 2018. Data was collected from the medical record database using a predesigned proforma. RESULTS: Of the 50 cases, 2(4%) were children and 48 (96%) were adults, with overall age ranging from 12 to 85 years. There were 41(82%) males and 9(18%) females.. Of the total, 30(60%) cases presented with type 1 reaction and 20(40%) with type 2. Further, 30(60%) cases were classified as borderline lepromatous. Among them, 17(57%) had type 2 reaction. Inflamed plaques were the main feature in 27(90%) cases of type 1. Crops of painful, erythematous nodules were seen in 19(95%) cases of type 2. CONCLUSION: Lepra reactions were found to be a presenting feature in a significant number of new leprosy cases at initial diagnosis.
Assuntos
Hanseníase , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Etnicidade , Feminino , Humanos , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To analyse the association between social inequalities and the leprosy burden in a low endemicity scenario in the state of São Paulo, Brazil. METHODS: This ecological study was carried out in the city of Ribeirão Preto, state of São Paulo, Brazil, considering leprosy cases notified from 2006 to 2016. Regarding social inequalities, dimensions related to high household density, literacy, home occupation conditions, health conditions, household income, ethnicity and age were considered. The generalised additive model for location, scale and shape (GAMLSS) was used to verify the association between the social inequalities and leprosy burden. RESULTS: The increase in men and women with no education and people with an income of 1 to 2 minimum wages was associated with a relative increase in the number of leprosy cases (7.37%, 7.10% and 2.44%, respectively). Regarding the ethnicity variables, the increase in the proportion of men (black) and women (mixed race) with no schooling was associated with a relative increase in the number of cases of the disease (10.77% and 4.02%, respectively). Finally, for people of mixed race or ethnicity, the increase in the proportion of households with 1/2 to 1 minimum wage was related to a relative decrease in the total number of cases (-4.90%). CONCLUSION: The results show that the determinants associated with the increase in leprosy cases are similar to those in Brazilian hyperendemic regions, and that even in cities with low endemicity, social inequality is one of the main determinants of the disease.
Assuntos
Doenças Endêmicas/estatística & dados numéricos , Hanseníase/epidemiologia , Fatores Socioeconômicos , Adulto , Brasil/epidemiologia , Brasil/etnologia , Cidades/epidemiologia , Cidades/etnologia , Escolaridade , Meio Ambiente , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Hanseníase/etnologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Leprosy is a prevalent disease in Brazil, which ranks as the country with the second highest number of cases in the world. The disease manifests in a spectrum of forms, and genetic differences in the host can help to elucidate the immunopathogenesis. For a better understanding of MICA association with leprosy, we performed a case-control and a family-based study in two endemic populations in Brazil. MICA and HLA-B alleles were evaluated in 409 leprosy patients and in 419 healthy contacts by PCR-SSOP-Luminex-based technology. In the familial study, analysis of 46 families was completed by direct sequencing of all exons and 3'/5'untranslated regions, using the Ilumina MiSeq platform. All data were collected between 2006 and 2009. Statistical analysis was performed using the Chi-square or Fisher's exact test together with a multivariate analysis. Family-based association was assessed by transmission disequilibrium test (TDT) software FBAT 2.0.4. We found associations between the haplotype MICA*002-HLA-B*35 with leprosy in both the per se and the multibacillary (MB) forms when compared to healthy contacts. The MICA allele *008 was associated with the clinical forms of paucibacillary (PB). Additionally, MICA*029 was associated with the clinical forms of MB. The association of MICA*029 allele (MICA-A4 variant) with the susceptibility to the MB form suggests this variant for the transmembrane domain of the MICA molecule may be a risk factor for leprosy. Two MICA and nine HLA-B variants were found associated with leprosy per se in the Colônia do Prata population. Linkage disequilibrium analysis revealed perfect linkage disequilibrium (LD) between HLA-B markers rs2596498 and rs2507992, and high LD (R2 = .92) between these and the marker rs2442718. This familial study demonstrates that MICA association signals are not independent from those observed for HLA-B. Our findings contribute the knowledge pool of the immunogenetics of Hansen's disease and reveals a new association of the MICA*029 allele.
Assuntos
Antígenos HLA-B/genética , Antígenos de Histocompatibilidade Classe I/genética , Hanseníase/imunologia , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas/genética , Adolescente , Adulto , Alelos , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Doenças Endêmicas , Etnicidade/genética , Éxons/genética , Saúde da Família , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos/genética , Humanos , Hanseníase/epidemiologia , Hanseníase/genética , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Domínios Proteicos , Adulto JovemRESUMO
Rosacea is a relatively common inflammatory dermatosis in persons with fair skin. It is uncommonly reported in people with skin of color (darker skin tone; Fitzpatrick skin types IV, V or VI). Apart from reduced incidence, underreporting due to decreased awareness might also be a probable explanation. Rosacea commonly presents with telangiectasias and persistent facial erythema on the sun-exposed parts, which can be distressing to the patient and affect the quality of life. The diagnosis is made clinically, in the absence of any confirmatory investigation. Several treatment modalities have been employed to date with varying results. Light-based therapies should be used cautiously in the colored skin to avoid distressing pigmentation. This article focuses on the pathogenesis, clinical features, treatment recommendations and other aspects of this uncommon disorder along with a review of the literature.
Assuntos
Rosácea , Etnicidade , Humanos , Índia , Rosácea/diagnóstico , Rosácea/etnologia , Rosácea/terapia , Pigmentação da PeleRESUMO
Few investigations to date have analyzed the epidemiology of Hansen's disease (leprosy) in the United States, and in particular, if birth location is related to multibacillary versus paucibacillary leprosy. We collected data on 123 patients diagnosed with leprosy in Georgia from the National Hansen's Disease Program from 1923-January 2018. A logistic regression model was built to examine the relationship between country of origin (U.S.-born or immigrant) and the type of leprosy. While the model showed no significant relationship between country of origin and type of leprosy, being Asian or Pacific Islander was associated with a higher odds of multibacillary disease (aOR = 5.71; 95% CI: 1.25-26.29). Furthermore, since the early 1900s, we found an increasing trend of leprosy reports in Georgia among both domestic born and immigrant residents, despite the overall decrease in cases in the United States during the same time period. More research is therefore necessary to further evaluate risk for multibacillary leprosy in certain populations and to create targeted interventions and prevention strategies.
Assuntos
Hanseníase/epidemiologia , Hanseníase/história , Emigrantes e Imigrantes , Etnicidade , Feminino , Georgia/epidemiologia , História do Século XX , História do Século XXI , Humanos , Hanseníase/prevenção & controle , Hanseníase Multibacilar/epidemiologia , Hanseníase Multibacilar/história , Hanseníase Multibacilar/prevenção & controle , Hanseníase Paucibacilar/epidemiologia , Hanseníase Paucibacilar/história , Hanseníase Paucibacilar/prevenção & controle , Masculino , Estados UnidosRESUMO
BACKGROUND: Although leprosy is largely curable with multidrug therapy, incomplete treatment limits therapeutic effectiveness and is an important obstacle to disease control. To inform efforts to improve treatment completion rates, we aimed to identify the geographic and socioeconomic factors associated with leprosy treatment default in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Using individual participant data collected in the Brazilian national registries for social programs and notifiable diseases and linked as part of the 100 Million Brazilian Cohort, we evaluated the odds of treatment default among 20,063 leprosy cases diagnosed and followed up between 2007 and 2014. We investigated geographic and socioeconomic risk factors using a multivariate hierarchical analysis and carried out additional stratified analyses by leprosy subtype and geographic region. Over the duration of follow-up, 1,011 (5.0%) leprosy cases were observed to default from treatment. Treatment default was markedly increased among leprosy cases residing in the North (OR = 1.57; 95%CI 1.25-1.97) and Northeast (OR = 1.44; 95%CI 1.17-1.78) regions of Brazil. The odds of default were also higher among cases with black ethnicity (OR = 1.29; 95%CI 1.01-1.69), no income (OR = 1.41; 95%CI 1.07-1.86), familial income ≤ 0.25 times Brazilian minimum wage (OR = 1.42; 95%CI 1.13-1.77), informal home lighting/no electricity supply (OR = 1.53; 95%CI 1.28-1.82), and household density of > 1 individual per room (OR = 1.35; 95%CI 1.10-1.66). CONCLUSIONS: The findings of the study indicate that the frequency of leprosy treatment default varies regionally in Brazil and provide new evidence that adverse socioeconomic conditions may represent important barriers to leprosy treatment completion. These findings suggest that interventions to address socioeconomic deprivation, along with continued efforts to improve access to care, have the potential to improve leprosy treatment outcomes and disease control.
Assuntos
Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Fatores Socioeconômicos , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Brasil/epidemiologia , Estudos de Coortes , Quimioterapia Combinada/estatística & dados numéricos , Etnicidade , Feminino , Geografia , Humanos , Hanseníase/epidemiologia , MasculinoRESUMO
Genome-wide association studies (GWASs) and genome-wide linkage studies (GWLSs) have identified numerous risk genes affecting the susceptibility to leprosy. However, most of the reported GWAS hits are noncoding variants and account for only part of the estimated heritability for this disease. In order to identify additional risk genes and map the potentially functional variants within the GWAS loci, we performed a three-stage study combining whole-exome sequencing (WES; discovery stage), targeted next-generation sequencing (NGS; screening stage), and refined validation of risk missense variants in 1,433 individuals with leprosy and 1,625 healthy control individuals from Yunnan Province, Southwest China. We identified and validated a rare damaging variant, rs142179458 (c.1045G>A [p.Asp349Asn]) in HIF1A, as contributing to leprosy risk (p = 4.95 × 10-9, odds ratio [OR] = 2.266). We were able to show that affected individuals harboring the risk allele presented with multibacillary leprosy at an earlier age (p = 0.025). We also confirmed the association between missense variant rs3764147 (c.760A>G [p.Ile254Val]) in the GWAS hit LACC1 (formerly C13orf31) and leprosy (p = 6.11 × 10-18, OR = 1.605). By using the population attributable fraction, we have shown that HIF1A and LACC1 are the major genes with missense variants contributing to leprosy risk in our study groups. Consistently, mRNA expression levels of both HIF1A and LACC1 were upregulated in the skin lesions of individuals with leprosy and in Mycobacterium leprae-stimulated cells, indicating an active role of HIF1A and LACC1 in leprosy pathogenesis.
Assuntos
Povo Asiático/genética , Etnicidade/genética , Predisposição Genética para Doença , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hanseníase/genética , Mutação de Sentido Incorreto/genética , Proteínas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Criança , Estudos de Coortes , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Fatores de Risco , Transativadores/genética , Regulação para Cima/genética , Sequenciamento do Exoma , Adulto JovemRESUMO
Darwinian medicine, or evolutionary medicine, regards some pathological conditions as attempts by the organism to solve a problem or develop defense mechanisms. At certain stages of human evolution, some diseases may have conferred a selective advantage. Psoriasis is a high-penetrance multigenic disorder with prevalence among whites of up to 3%. Psoriatic lesions have been linked with enhanced wound-healing qualities and greater capacity to fight infection. Leprosy, tuberculosis, and infections caused by viruses similar to human immunodeficiency virus have been postulated as environmental stressors that may have selected for psoriasis-promoting genes in some human populations. The tendency of patients with severe psoriasis to develop metabolic syndrome may reflect the body's attempt to react to environmental stresses and warning signs by triggering insulin resistance and fat storage.
Assuntos
Evolução Biológica , Aptidão Genética , Psoríase/genética , Adaptação Biológica , Peso ao Nascer , Metabolismo Energético , Etnicidade/genética , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Síndrome Metabólica/etiologia , Penetrância , Psoríase/complicações , Psoríase/epidemiologia , Psoríase/fisiopatologia , Seleção Genética , Dermatopatias Infecciosas/genética , Dermatopatias Infecciosas/prevenção & controle , CicatrizaçãoRESUMO
BACKGROUND: The color of Indian skin shows great diversity and pigmentary disorders are a major concern of Indian women. Despite great variations in climate, diet, and social parameters within India, studies of the range of skin types have been rather scarce. AIMS: This study was aimed at characterizing the color of Indian skin in various geographical locations, its characteristics in terms of overall skin complexion and pigmentary disorders, and the impact of age on these features. METHODS: An extensive descriptive study, including skin color parameters (objective measurements and evaluations by dermatologists, clinically or from photographs) was carried out involving 1,204 female volunteers of different ages living in four different Indian cities. RESULTS: Important differences in skin complexion according to the geographical location were observed. Age seemed to have little impact on complexion. Hyperpigmented spots were frequent and were noted at early stages and many lentigines were found. Melasma affected about 30% of middle-aged women, but many other ill defined, pigmented macules were also observed. Additionally, we found pigmented lip corners associated with marionette lines, and linear nasal pigmentation. CONCLUSIONS: Indian skin color is diverse and pigmentary disorders are common. Skin complexion is not greatly affected by age. Some hyperpigmented disorders occur at early stages and increase with age, contributing to overall unevenness of facial color.
Assuntos
Transtornos da Pigmentação/etnologia , Pigmentação da Pele/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Etnicidade , Feminino , Humanos , Índia/epidemiologia , Pessoa de Meia-Idade , Características de Residência , Adulto JovemAssuntos
Etnicidade , Dermatopatias/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Infecções/epidemiologia , MasculinoRESUMO
The purpose of this study was to determine whether interleukin-10 (IL-10) promoter polymorphisms are associated with leprosy or their subtypes in ethnic groups from southwest China. Genotyping using TaqMan® SNP Genotyping Master Mix and ABI 7500 real-time PCR system was performed for IL-10 T3575A, G2849A, C2763A, A1082G, C819T, and C592A in 189 healthy controls (40 ± 18 years) and 193 patients (46 ± 18 years) with leprosy [multibacillary, N = 131; paucibacillary (PB), N = 62]. The allelic frequencies of -2763C (97.9 vs 94.0%, P = 0.0074) and -1082A (92.8 vs 88.6%, P = 0.0452) in leprosy patients were significantly higher than in control subjects. The genetic frequency of -2763CC and -1082AA was not only significantly higher among leprosy patients than among control subjects [odds ratio (OR) = 3.33, 95% confidence interval (95%CI) = 1.39-7.99, P = 0.0071 and OR = 1.76, 95%CI = 1.02-3.03, P = 0.0420, respectively] but also significantly higher among PB patients than among control subjects (OR = 2.46, 95%CI = 1.22-4.96, P = 0.0115 and OR = 5.58, 95%CI = 2.06-15.12, P = 0.0007, respectively). The frequency of IL-10 haplotype 3575A/2849G/2763A/1082G/819C/592C was significantly higher among leprosy patients (OR = 5.57, 95%CI = 1.13-27.52, P = 0.0351) and PB patients (OR = 10.5, 95%CI = 1.36- 81.05, P = 0.0241) than among control subjects. IL-10 promoter -2763C/CC,-1082A/AA and haplotype 3575A/2849G/2763A/1082 G/819C/592C are associated with susceptibility to leprosy and the PB subtype in southwest China.
Assuntos
Suscetibilidade a Doenças , Interleucina-10/genética , Hanseníase/genética , Regiões Promotoras Genéticas/genética , Adolescente , Adulto , Povo Asiático , China , Etnicidade/genética , Feminino , Haplótipos , Humanos , Hanseníase/patologia , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
One of the persistent challenges of genetic association studies is the replication of genetic marker-disease associations across ethnic groups. Here, we conducted high-density association mapping of PARK2/PACRG SNPs with leprosy and identified 69 SNPs significantly associated with leprosy in 198 single-case Vietnamese leprosy families. A total of 56 associated SNPs localized to the overlapping promoter regions of PARK2/PACRG. For this region, multivariate analysis identified four SNPs belonging to two major SNP bins (rs1333955, rs7744433) and two single SNP bins (rs2023004, rs6936895) that capture the combined statistical evidence (P = 1.1 × 10(-5)) for association among Vietnamese patients. Next, we enrolled a case-control sample of 364 leprosy cases and 370 controls from Northern India. We genotyped all subjects for 149 SNPs that capture >80 % of the genetic variation in the Vietnamese sample and found 24 SNPs significantly associated with leprosy. Multivariate analysis identified three SNPs (rs1333955, rs9356058 and rs2023004) that capture the association with leprosy (P < 10(-8)). Hence, two SNPs (rs1333955 and rs2023004) were replicated by multivariate analysis between both ethnic groups. Marked differences in the linkage disequilibrium pattern explained some of the differences in univariate analysis between the two ethnic groups. In addition, the strength of association for two promoter region SNP bins was significantly stronger among young leprosy patients in the Vietnamese sample. The same trend was observed in the Indian sample, but due to the higher age-at-diagnosis of the patients the age effect was less pronounced.
Assuntos
Etnicidade/genética , Hanseníase/genética , Chaperonas Moleculares/genética , Ubiquitina-Proteína Ligases/genética , Adolescente , Adulto , Idade de Início , Povo Asiático/genética , Estudos de Casos e Controles , Criança , Feminino , Estudos de Associação Genética , Humanos , Índia , Íntrons , Hanseníase/diagnóstico , Desequilíbrio de Ligação , Masculino , Proteínas dos Microfilamentos , Pessoa de Meia-Idade , Análise Multivariada , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Vietnã , População Branca/genética , Adulto JovemRESUMO
INTRODUCTION: Polymorphisms in promoters of genes code for cytokines that affect transcription levels. Several have been associated with leprosy patients that have functional and clinical implications. OBJECTIVE: Polymorphisms in the promoter of the IL10 gene of leprosy patients will be compared frequencies in normal population. MATERIALS AND METHODS: SNPs (single nucleotide polymorphism) -1082 A/G (rs1800896), -819C/T (rs1800871), and -592A/C (rs1800872) were identified in 100 leprosy patients and in a control group of 100 volunteers from a leprosy endemic region of Colombia. RESULTS: The genotypes C/C and C/T in the SNP -819 were associated together with leprosy (OR=4.34, p<0.001).Similarly, the genotypes C/C and C/A in the -592 SNP showed an association (OR=4.3, p<0.001). The haplotypes -819C-519C and -1082A-819C-592C showed significant association (OR=4.34, p<0.001 and OR=6.25, p<0.001) respectively. These haplotypes in homozygosis conditions were also associated with leprosy: -819C-519C/-819C-519C (OR=4.34, p<0.001), -1082A -819C-592C/-1082A -819C-592C (OR=1.90, p=0.04). The SNP -1082 was not associated with leprosy in this population. CONCLUSIONS: The haplotypes associated with leprosy, -1082A-819C-592C/-1082A-819C-592C, have been reported as low producers of IL-10. Functionally, the low production of IL-10 may have immune response consequences and clinical implications. Additional haplotypes of IL-10 have been reported as markers for leprosy susceptibility or resistance in other ethnic populations. This suggests that differences in distribution of diverse IL-10 gene polymorphisms among ethnic groups may indicate important gene-disease associations.
Assuntos
Interleucina-10/genética , Hanseníase/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Colômbia/epidemiologia , Doenças Endêmicas , Etnicidade/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Interleucina-10/biossíntese , Interleucina-10/fisiologia , Hanseníase/epidemiologia , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/isolamento & purificação , População Branca/genética , Adulto JovemRESUMO
BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an unculturable pathogen with an exceptionally eroded genome. The high level of inactivation of gene function in M. leprae, including many genes in its metabolic pathways, has led to a dependence on host energy production and nutritional products. We hypothesized that host cellular powerhouse--the mitochondria--may affect host susceptibility to M. leprae and the onset of clinical leprosy, and this may be reflected by mitochondrial DNA (mtDNA) background and mtDNA copy number. METHODS: We analyzed the mtDNA sequence variation of 534 leprosy patients and 850 matched controls from Yunnan Province and classified each subject by haplogroup. mtDNA copy number, taken to be proportional to mtDNA content, was measured in a subset of these subjects (296 patients and 231 controls) and 12 leprosy patients upon diagnosis. RESULTS: Comparison of matrilineal components of the case and control populations revealed no significant difference. However, measurement of mtDNA copy number showed that lepromatous leprosy patients had a significantly higher mtDNA content than controls (P = 0.008). Past medical treatments had no effect on the alteration of mtDNA copy number. CONCLUSIONS: Our results suggested that mtDNA content, but not haplogroup, affects leprosy and this influence is limited to the clinical subtype of lepromatous leprosy.
Assuntos
DNA Mitocondrial/genética , Etnicidade/genética , Dosagem de Genes , Predisposição Genética para Doença , Hanseníase/genética , Sequência de Bases , Estudos de Casos e Controles , China , Primers do DNA , HumanosRESUMO
Introduction. Polymorphisms in promoters of genes code for cytokines that affect transcription levels. Several have been associated with leprosy patients that have functional and clinical implications. Objective. Polymorphisms in the promoter of the IL10 gene of leprosy patients will be compared frequencies in normal population. Materials and methods. SNPs (single nucleotide polymorphism) -1082 A/G (rs1800896), -819C/T (rs1800871), and -592A/C (rs1800872) were identified in 100 leprosy patients and in a control group of 100 volunteers from a leprosy endemic region of Colombia. Results. The genotypes C/C and C/T in the SNP -819 were associated together with leprosy (OR=4.34, p<0.001).Similarly, the genotypes C/C and C/A in the -592 SNP showed an association (OR=4.3, p<0.001). The haplotypes -819C-519C and -1082A-819C-592C showed significant association (OR=4.34, p<0.001 and OR=6.25, p<0.001) respectively. These haplotypes in homozygosis conditions were also associated with leprosy: -819C-519C/-819C-519C (OR=4.34, p<0.001), -1082A -819C-592C/-1082A -819C-592C (OR=1.90, p=0.04). The SNP -1082 was not associated with leprosy in this population. Conclusions. The haplotypes associated with leprosy, -1082A-819C-592C/-1082A-819C-592C, have been reported as low producers of IL-10. Functionally, the low production of IL-10 may have immune response consequences and clinical implications. Additional haplotypes of IL-10 have been reported as markers for leprosy susceptibility or resistance in other ethnic populations. This suggests that differences in distribution of diverse IL-10 gene polymorphisms among ethnic groups may indicate important gene-disease associations.
Introducción. Se han reportado polimorfismos en los genes promotores que codifican para citocinas y que afectan los niveles de transcripción, con implicaciones clínicas y funcionales en pacientes con lepra. Objetivo. Detectar los polimorfismos en el gen promotor de la interleucina 10 (IL-10), de los polimorfismos de un solo nucleótido (Single Nucleotide Polymorphisms, SNP) -1082 A/G (rs1800896), -819C/T (rs1800871) y -592A/C (rs1800872), en 100 pacientes con lepra y un grupo control de 100 voluntarios, de una región endémica de Colombia. Resultados. Los haplotipos -819C-519C y -1082A-819C-592C mostraron asociación significativa con lepra: OR=4,34, p=1 x 10-3, y OR=6,25, p=5 x 10-4, respectivamente. Estos haplotipos en condiciones de homocigoto, están también asociados con lepra: -819C-519C/-819C-519C (OR=4,34 p=1 x 10-3), -1082A -819C-592C/-1082A -819C-592C (OR=1,90 y p=0,04). El SNP -1082 no se encontró asociado con lepra en esta población. Los genotipos C/C y C/T en el SNP -819, se encontraron asociados a lepra (OR=4,34, p=1 x 10-3); de igual manera, los genotipos C/C y C/A en el SNP -592 mostraron asociación (OR=4,34, p=1 x 10-3). Conclusiones. El haplotipo que encontramos asociado con lepra, -1082A-819C-592C/-1082A-819C-592C, se ha relacionado con baja producción de IL-10. Funcionalmente, esta baja producción de IL-10 puede tener consecuencias en la respuesta inmunitaria, además de implicaciones clínicas. Se han reportado diferentes haplotipos de IL-10 como marcadores de vulnerabilidad y resistencia de lepra en otras poblaciones, lo cual sugiere que las diferencias en la distribución de diversos polimorfismos del gen de IL-10 entre grupos étnicos, es un factor importante al determinar la asociación entre enfermedad y genes.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , /genética , Hanseníase/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Estudos de Casos e Controles , Colômbia/epidemiologia , Doenças Endêmicas , Etnicidade/genética , População Branca/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , /biossíntese , /fisiologia , Hanseníase/epidemiologia , Hanseníase/microbiologia , Mycobacterium leprae/isolamento & purificaçãoAssuntos
Modificação Corporal não Terapêutica/efeitos adversos , Cicatriz/etnologia , Cicatriz/patologia , Etnicidade/estatística & dados numéricos , Modificação Corporal não Terapêutica/estatística & dados numéricos , Feminino , Humanos , Infecções/etnologia , Masculino , Nigéria/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Human leukocyte antigens (HLAs) have been proposed to modulate the immune response to Mycobacterium leprae. The association of HLA-DRB1 with leprosy has been reported in several populations, but not in a Chinese population. METHODS: The polymerase chain reaction-sequence-specific oligonucleotide probe with Luminex100 (PCR-SSOP-Luminex) method was used to genotype HLA-DRB1 alleles in 305 leprosy patients and 527 healthy control individuals. RESULTS: The HLA-DRB1*15 allele was significantly more prevalent among leprosy patients than healthy controls, whereas the frequency of the HLA-DRB1*09 allele was lower among leprosy patients, especially those with early-onset disease. CONCLUSION: HLA-DRB1 alleles are associated with leprosy susceptibility in a Chinese population. The HLA-DRB1*09 allele was found to be protective exclusively in a subset of early-onset leprosy patients.
Assuntos
Antígenos HLA-DR/genética , Hanseníase/genética , Idade de Início , Idoso , Alelos , Estudos de Casos e Controles , China/epidemiologia , Etnicidade , Feminino , Frequência do Gene , Estudos de Associação Genética , Cadeias HLA-DRB1 , Humanos , Hanseníase/epidemiologia , Hanseníase Multibacilar/epidemiologia , Hanseníase Multibacilar/genética , Hanseníase Paucibacilar/epidemiologia , Hanseníase Paucibacilar/genética , Masculino , Adulto JovemRESUMO
OBJECTIVE: To determine whether cytokine polymorphisms are associated with leprosy and/or their subtypes in a Brazilian population. METHODS: Genotyping using polymerase chain reaction with sequence-specific primers (PCR-SSP) was performed for: TNF(-308/-238), IL2(-330/+166), IL6(-174), IFNG(+874), TGFB1(+869/+915), and IL10(-592/-819/-1082) in 240 healthy controls and 167 patients with leprosy. RESULTS: For TNF(-308), a higher frequency of GG genotype (85.5% vs. 74.1% in healthy controls, p = 0.009), along with a decreased frequency of GA/AA genotypes was observed among leprosy patients as compared to the control group (14.5% vs. 25.9%, p = 0.009). The GG genotype was particularly higher in patients with tuberculoid (TT) and borderline (BB) leprosy (90.5% and 89.8%, respectively). Analysis of IL10 genotypes revealed a lower frequency of GCC/GCC haplotype in lepromatous leprosy (LL) patients (6.2%) in comparison to controls (15.4%). CONCLUSION: It is suggested that the G-->A substitution at position -308 in the TNF promoter region plays an important role in leprosy patients.
Assuntos
Interleucina-10/genética , Hanseníase/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Brasil/epidemiologia , Etnicidade , Feminino , Frequência do Gene , Genótipo , Humanos , Hanseníase/epidemiologia , Hanseníase/imunologia , Masculino , Reação em Cadeia da Polimerase , Valores de ReferênciaRESUMO
AIM: To study the clinical and immunological profile in patients of systemic sclerosis from North India and compare it with other ethnic groups. METHODS: Patients presenting to us between the years 2001 and 2004 and fulfilling the American Rheumatism Association (ARA) criteria for systemic sclerosis were included. There were 84 females and 16 males with the mean age of 32.5 +/-11.62 years and a mean duration of 6.49 +/- 4.34 years. All patients were admitted to the dermatology ward for detailed history and examination including Rodnan score. Investigations including hemogram, hepatic and renal functions, serum electrolytes, urine for albumin, sugar, microscopy and 24h urinary protein estimation, antinuclear antibody, chest X-ray, barium swallow, pulmonary function test, electrocardiogram and skin biopsy were done. RESULTS: The most common presenting symptoms were skin binding-down (98.5%), Raynaud's phenomenon 92.9%, pigmentary changes 91%, contracture of fingers 64.6%, fingertip ulcer 58.6%, restriction of mouth opening 55.5%, dyspnea 51.1%, joint complaints 36.7% and dysphagia in 35.2%. The mean Rodnan score was 25.81 +/- 10.04 and the mean mouth opening was 24.6 +/- 19.01 mm. The laboratory abnormalities included raised ESR in 87.8%, ANA positive in 89.1%, proteinuria in 6.0%, abnormal chest X-ray in 65.3%, abnormal barium swallow in 70.2% and reduced pulmonary function test in 85.8%. CONCLUSION: The clinical and immunological profile of systemic sclerosis in North India is similar to that of other ethnic groups except that pigmentary changes are commoner and renal involvement is relatively uncommon.