RESUMO
El manejo del síndrome de abstinencia alcohólica es un desafío en los pacientes críticos. Con frecuencia, se desconocen los antecedentes de consumo de alcohol o este dato es incompleto, lo que limita la identificación de quienes pueden desarrollar este síndrome. El cese abrupto del consumo de alcohol coloca a estos pacientes en alto riesgo de sufrir síndrome de abstinencia alcohólica grave. Típicamente, las benzodiacepinas son consideradas las drogas de primera línea para el manejo de estos casos. Sin embargo, si el paciente progresa a un estado más grave con convulsiones o delirium tremens, puede ser necesario administrar medicación adyuvante a las benzodiacepinas, como el propofol o la dexmedetomidina, o emplear estas últimas drogas como terapias alternativas en aquellos que no responden a las benzodiacepinas. La aparición de convulsiones representa un fuerte factor de riesgo para la progresión a un síndrome de abstinencia alcohólica grave, con el desarrollo posterior de delirium tremens hasta en el 30% de los casos. El delirium tremens es el cuadro más grave y ocurre en el 5-20% de los pacientes con este síndrome, con una mortalidad hasta del 25% sin tratamiento y que se reduce al 0-1% con tratamiento. Es importante conocer el antecedente del consumo de alcohol para evitar el síndrome de abstinencia alcohólica o tratar rápidamente sus síntomas más graves, y mejorar la supervivencia de estos pacientes.(AU)
Alcohol withdrawal syndrome (AWS) is a well-known and a challenging condition occurring in critically ill patients. Frequently, history of alcohol abuse is unknown when the patient is admitted to the intensive care unit, limiting the identification of those who could develop AWS. The abrupt cessation of a heavy or constant drinking put these patients in high risk of suffering from this syndrome in its severe form. Typically, benzodiazepines are considered the first line of treatment. However, if clinical conditions progress to epileptic seizures or delirium tremens or are refractory to benzodiazepines, adjuvant drugs like propofol or dexmedetomidine might be an option to control the severe symptoms. Delirium tremens can occur in up to 30% of patients; it is the most severe picture with a mortality of 25% without treatment and that can be reduced to almost 0-1% with treatment. It is important to appropriately identify alcohol abuse in order to avoid the early clinical manifestations of AWS or rapidly treat its most severe symptoms and improve survival.(AU)
Assuntos
Humanos , Delirium por Abstinência Alcoólica/tratamento farmacológico , Abstinência de Álcool , Benzodiazepinas , Cuidados CríticosRESUMO
BACKGROUND: Microencapsulation of pancreatic islets with polymeric compounds constitutes an attractive alternative therapy for type 1 diabetes mellitus. The major limiting factor is the availability of a biocompatible and mechanically stable polymer. We investigated the potential of Biodritin, a novel polymer constituted of alginate and chondroitin sulfate, for islet microencapsulation. METHODS: Biodritin microcapsules were obtained using an air jet droplet generator and gelated with barium or calcium chloride. Microencapsulated rat insulinoma RINm5F cells were tested for viability using the [3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide] [MTT] colorimetric assay. Microencapsulated rat pancreatic islets were coincubated with macrophages derived from mouse peritoneal liquid to assess the immunomodulatory potential of the microcapsules, using quantitative real time-PCR (qPCR). Biodritin biocompatibility was demonstrated by subcutaneous injection of empty microcapsules into immunocompetent Wistar rats. Insulin secretion by microencapsulated human pancreatic islets was evaluated using an electrochemoluminescent assay. Microencapsulated human islets transplanted into chemically induced diabetic mice were monitored for reversal of hyperglycemia. RESULTS: The metabolic activity of microencapsulated RINm5F cells persisted for at least 15 days. Interleukin-1beta expression by macrophages was observed during coculture with islets microencapsulated with Biodritin-CaCl2, but not with Biodritin-BaCl2. No statistical difference in glucose-stimulated insulin secretion was observed between nonencapsulated and microencapsulated islets. Upon microencapsulated islet transplantation, the blood glucose level of diabetic mice normalized; they remained euglycemic for at least 60 days, displaying normal oral glucose tolerance tests. CONCLUSION: This study demonstrated that Biodritin can be used for islet microencapsulation and reversal of diabetes; however, further investigations are required to assess its potential for long-term transplantation.
Assuntos
Alginatos/farmacologia , Cápsulas , Sulfatos de Condroitina/farmacologia , Diabetes Mellitus Tipo 1/cirurgia , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/fisiologia , Animais , Materiais Biocompatíveis , Linhagem Celular Tumoral , Técnicas de Cocultura , Humanos , Insulina/metabolismo , Secreção de Insulina , Insulinoma , Ilhotas Pancreáticas/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/fisiologia , RatosRESUMO
Autoimmune hepatitis is an immune cell-mediated chronic liver disease of unknown cause that leads, when untreated, to cirrhosis and liver failure. Importantly, this disease affects not only adults but children as well. Genetic susceptibility is clearly important and the major susceptibility factor identified up to now is the HLA-DRB1 locus, but other genes may play a role as well. HLA-DRB1 alleles present in South American patients differ from those found in patients in other parts of the world. In addition, we have recently identified two chromosomal regions where additional susceptibility factors may be found in Brazilian patients, namely, the class III MHC region and the 5q31 region where the IL-4 and IL-13 genes are located. This review discusses the current knowledge of the pathogenesis of this autoimmune disease occurring in the setting of an immune-privileged organ, the liver, and compares the data on gene polymorphisms studied in Brazil and in other parts of the world.
Assuntos
Hepatite Autoimune/epidemiologia , Hepatite Autoimune/imunologia , Brasil/epidemiologia , Hepatite Autoimune/classificação , Hepatite Autoimune/genética , HumanosRESUMO
Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.
Assuntos
Antígenos HLA-DR/genética , Lúpus Eritematoso Sistêmico/genética , Adolescente , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Cadeias HLA-DRB1 , Teste de Histocompatibilidade , Humanos , Lactente , Nefropatias/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Masculino , Reação em Cadeia da PolimeraseRESUMO
Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Antígenos HLA-DR/genética , Lúpus Eritematoso Sistêmico/genética , Ensaio de Imunoadsorção Enzimática , Teste de Histocompatibilidade , Nefropatias/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Reação em Cadeia da PolimeraseRESUMO
Ex vivo islet cell culture prior to transplantation appears as an attractive alternative for treatment of type 1 diabetes. Previous results from our laboratory have demonstrated beneficial effects of human prolactin (rhPRL) treatment on human islet primary cultures. In order to probe into the molecular events involved in the intracellular action of rhPRL in these cells, we set out to identify proteins with altered expression levels upon rhPRL cell treatment, using two-dimensional (2D) gel electrophoresis and mass spectrometry (MS). An average of 300 different protein spots were detected, 14 of which were modified upon rhPRL treatment (p<0.01), of which 12 were successfully identified using MS and grouped according to their biological functions. In conclusion, our study provides, for the first time, information about proteins that could be critically involved in PRL's action on human pancreatic islets, and facilitate identification of new and specific targets involved in islet cell function and proliferation.
Assuntos
Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Prolactina/farmacologia , Adulto , Eletroforese em Gel Bidimensional , Feminino , Humanos , Ilhotas Pancreáticas/citologia , Transplante das Ilhotas Pancreáticas , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/farmacologia , Técnicas de Cultura de TecidosRESUMO
Propósito: reseñar los hallazgos clínicos y ecográficos obtenidos durante 16 años del estudio de 159 pacientes, en quienes se diagnosticó transformación cavernomatosa de la vena porta (TCVP) e hipertensión portal (HP). Material y Métodos: Evaluamos los registros de 159 pacientes a los que se les diagnosticó TCVP durante el período 1987 -2003, consignando los datos referidos al cuadro clínico de presentación, patologías asociadas, los signos ultrasonográficos (US) morfológicos hallados al diagnóstico, su prevalencia y las relaciones entre las diferentes variables. Resultados: Los hallazgos clínicos más significativos fueron sangrado gastrointestinal y esplenomegalia. La imagen US, se caracteriza por múltiples estructuras anecoicas tortuosas, que reemplazan la imagen ecográfica caracteristica de la vena porta, ella permite realizar el diagnóstico inmediato y preciso de TCVP. Los principales signos US de HP hallados fueron: esplenomegalia (71,6 por ciento el bazo fue de tamaño normal en el 28,3 por ciento) y relación epiplon menor /aorta aumentada (69 ,1 por ciento). Circulación colateral: vena coronaria en epiplon menor (44 por ciento), venas colaterales dorsales (28.9 por ciento), várices vasiculares (36,8 por ciento), várices hemorroidales ( 8.8 por ciento). Ascitis (9.4 por ciento). El tamaño hepático se observó disminuido en el 32.6 por ciento de los pacientes. Conclusión: la TCVP y la HP secundaria a la misma, en la actualidad, son entidades que pueden ser diagnosticadas mediante la exploración US morfológica. La utilización de otros métodos de imágenes de mayor complejidad, en los pacientes pediátricos, debe estar supeditada a la necesidad de información complementaria relacionada con la toma de decisiones quirúrgicas
Assuntos
Lactente , Pré-Escolar , Criança , Adolescente , Ultrassonografia , Hipertensão Portal/diagnóstico , Veia Porta/patologiaRESUMO
Paramyosin, a Schistosoma mansoni myoprotein associated with human resistance to infection and reinfection, is a candidate antigen to compose a subunit vaccine against schistosomiasis. In this study, 11 paramyosin peptides selected by TEPITOPE algorithm as promiscuous epitopes were produced synthetically and tested in proliferation and in vitro human leucocyte antigen (HLA)-DR binding assays. A differential proliferative response was observed in individuals resistant to reinfection compared to individuals susceptible to reinfection in response to Para (210-226) peptide stimulation. In addition, this peptide was able to bind to all HLA-DR molecules tested in HLA-DR binding assays, confirming its promiscuity. Para (6-22) and Para (355-371) were also shown to be promiscuous peptides, because they were able to bind to the six and eight most prevalent HLA-DR alleles used in HLA-DR binding assays, respectively, and were also recognized by T cells of the individuals studied. These results suggest that these paramyosin peptides are promising antigens to compose an anti-schistosomiasis vaccine.
Assuntos
Epitopos de Linfócito T/imunologia , Proteínas de Helminto/imunologia , Esquistossomose mansoni/imunologia , Tropomiosina/imunologia , Adolescente , Adulto , Idoso , Algoritmos , Antígenos de Helmintos/imunologia , Divisão Celular/imunologia , Criança , Feminino , Antígenos HLA-DR/imunologia , Humanos , Imunidade Celular/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Peptídeos/imunologia , Linfócitos T/imunologiaRESUMO
Familial amyloid polyneuropathy (FAP) is an inherited amyloidosis mainly associated with transthyretin Val30Met variant. Clinical heterogeneity has been reported in different populations with FAP and Va130Met variant. In order to characterize FAP expression in Brazilians and to compare its features to those reported in other cohorts, 44 Brazilian patients (27 females, median age 36 [23-53] years) with FAP and the Val30Met variant were investigated. Approximately 40% of their family members, with the exception, of parents and siblings, had FAP. Most of the patients had symptoms of peripheral neuropathy at onset. Median age at onset was 32 [20-44] years. Earlier onset was observed in males (27 [20-43] years in males vs. 33 [20-44] years in females, P = 0.02) and in patients whose parents had FAP (31 [20-44] years vs. 40 [37-43] years in patients, respectively with and without affected parents, P = 0.03). Phenotypic expression of FAP in Brazil is similar to the one reported in Portugal, characterized by high disease penetrance, early onset, particularly in males and in subjects with affected parents, and major symptoms of peripheral neuropathy. These data highlight the influence of common genetic factors, shared by both groups of patients, in disease expression.
Assuntos
Neuropatias Amiloides Familiares/genética , Mutação , Fenótipo , Pré-Albumina/genética , Adulto , Fatores Etários , Idade de Início , Neuropatias Amiloides Familiares/epidemiologia , Índice de Massa Corporal , Brasil/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Metionina/genética , Pessoa de Meia-Idade , Exame Neurológico , Valina/genéticaRESUMO
Diabetes mellitus is a widespread disease whose frequency increases constantly and is expected to reach alarming levels by the year 2025. Introduction of insulin therapy represented a major breakthrough; however, a very strict regimen is required to maintain blood glucose levels within the normal range and to prevent or postpone chronic complications associated with this disease. Frequent hyper- and hypoglycemia seriously affect the quality of life of these patients. Reversion of this situation can only be achieved through whole organ (pancreas) transplant or pancreatic islet transplant, the former being a high-risk surgical procedure, while the latter is a much simpler and may be accomplished in only 20-40 min. The advantages and perspectives of islet cell transplantation will be discussed, in the light of tissue engineering and gene therapy. Ongoing research carried out in our laboratory, aimed at developing clinical cell and molecular therapy protocols for diabetes will also be focused
Assuntos
Criança , Adolescente , Adulto , Humanos , Masculino , Feminino , Terapia Baseada em Transplante de Células e Tecidos , Diabetes Mellitus/cirurgia , Diabetes Mellitus/terapia , Transplante das Ilhotas Pancreáticas , Transplante de PâncreasRESUMO
The major histocompatibility complex (MHC) class I chain-related A (MICA) gene, located near HLA-B, codes for protein products with structural similarities to those of classical MHC class I genes, but which neither bind beta(2)-microglobulin nor present peptide. Expressed predominantly on gastrointestinal and tumour epithelial cells, they are stress-induced and interact with C-type lectin like receptor (NKG2D) on gammadelta, alphabeta CD8+ T cells and natural killer (NK) cells. MICA is highly polymorphic, with 54 extracellular allelic sequences described. We typed 200 healthy subjects in a sample of the São Paulo population by extended polymerase chain reaction-sequence-specific primers (PCR-SSP) to characterize the MICA polymorphism and analysed MICA/HLA-B linkage disequilibrium. The MICA*008 group (g) was predominant (47%), with several HLA-B associations. Rare combinations MICA*008g-HLA-B37, MICA*008g-B72 and MICA*010-HLA-B52 were detected. Given the extent of this polymorphism and its possible relevance for disease association, we determined MICA and HLA-B alleles in 33 Behçet's patients, in an attempt to clarify the associated genetic marker. Our results showed an increase of MICA*006, but not MICA*009, in the patient group (6/33) compared with controls (3/200) (18.2% vs. 1.5%; P(c) = 0.005). Both alleles were always in association with HLA-B51, suggesting that HLA-B is indeed the primary susceptibility locus (P = 0.00008) and that MICA*006 may be an additional risk factor.
Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo Genético , Brasil , Frequência do Gene , Genética Populacional , Antígenos HLA-B/genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Fenótipo , Reação em Cadeia da Polimerase/métodosAssuntos
Criança , Angioplastia , Constrição Patológica , Implantação de Prótese , Transplante de Fígado , Veia PortaRESUMO
The hypothesis of the role of iron overload associated with HFE gene mutations in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been raised in recent years. In the present study, biochemical and histopathological evidence of iron overload and HFE mutations was investigated in NASH patients. Thirty-two NASH patients, 19 females (59%), average 49.2 years, 72% Caucasians, 12% Mulattoes and 12% Asians, were submitted to serum aminotransferase and iron profile determinations. Liver biopsies were analyzed for necroinflammatory activity, architectural damage and iron deposition. In 31 of the patients, C282Y and H63D mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased in 30 patients, 2.42 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 31.3 g/dl, 33.1 12.7% and 219.8 163.8 g/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1% of the patients. Hepatic siderosis was observed in three patients and was not associated with architectural damage (P = 0.53) or with necroinflammatory activity (P = 0.27). The allelic frequencies (N = 31) found were 1.6 and 14.1% for C282Y and H63D, respectively, which were compatible with those described for the local population. In conclusion, no evidence of an association of hepatic iron overload and HFE mutations with NASH was found. Brazilian NASH patients comprise a heterogeneous group with many associated conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs, but not hepatic iron overload, and their disease susceptibility could be related to genetic and environmental features other than HFE mutations.
Assuntos
Fígado Gorduroso/etiologia , Antígenos de Histocompatibilidade Classe I/genética , Sobrecarga de Ferro/complicações , Proteínas de Membrana/genética , Mutação , Adulto , Idoso , Alanina Transaminase/análise , Biópsia , Estudos de Coortes , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Feminino , Ferritinas/análise , Proteína da Hemocromatose , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Transferrina/análiseRESUMO
The hypothesis of the role of iron overload associated with HFE gene mutations in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been raised in recent years. In the present study, biochemical and histopathological evidence of iron overload and HFE mutations was investigated in NASH patients. Thirty-two NASH patients, 19 females (59 percent), average 49.2 years, 72 percent Caucasians, 12 percent Mulattoes and 12 percent Asians, were submitted to serum aminotransferase and iron profile determinations. Liver biopsies were analyzed for necroinflammatory activity, architectural damage and iron deposition. In 31 of the patients, C282Y and H63D mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased in 30 patients, 2.42 + or - 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 + or - 31.3 g/dl, 33.1 + or - 12.7 percent and 219.8 + or - 163.8 æg/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1 percent of the patients. Hepatic siderosis was observed in three patients and was not associated with architectural damage (P = 0.53) or with necroinflammatory activity (P = 0.27). The allelic frequencies (N = 31) found were 1.6 and 14.1 percent for C282Y and H63D, respectively, which were compatible with those described for the local population. In conclusion, no evidence of an association of hepatic iron overload and HFE mutations with NASH was found. Brazilian NASH patients comprise a heterogeneous group with many associated conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs, but not hepatic iron overload, and their disease susceptibility could be related to genetic and environmental features other than HFE mutations
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fígado Gorduroso , Sobrecarga de Ferro , Mutação , Alanina Transaminase , Biópsia , Estudos de Coortes , Fígado Gorduroso , Ferritinas , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , TransferrinaAssuntos
Colangite Esclerosante/genética , Antígenos HLA-DR/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Brasil , Estudos de Casos e Controles , Criança , Feminino , Predisposição Genética para Doença , Cadeias HLA-DRB1 , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genéticaRESUMO
The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53%) were homozygous and one (7%) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil.
Assuntos
Antígenos HLA/genética , Antígenos HLA-A/genética , Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I/genética , Proteínas de Membrana , Mutação/genética , Adulto , Idade de Início , Idoso , Substituição de Aminoácidos , Sequência de Bases , Brasil/epidemiologia , Testes Genéticos , Hemocromatose/epidemiologia , Proteína da Hemocromatose , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53 percent) were homozygous and one (7 percent) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil