RESUMO
ABSTRACT Background. The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico. Material and methods. In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed. Results. The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p < 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p > 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p < 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-platelet-ratio-index score among HCV-patients. Conclusion. A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.
Assuntos
Humanos , Pessoa de Meia-Idade , Antivirais/efeitos adversos , Pirofosfatases/genética , Ribavirina/efeitos adversos , Polimorfismo de Nucleotídeo Único , Variantes Farmacogenômicos , Anemia Hemolítica/genética , Anemia Hemolítica/induzido quimicamente , Fenótipo , Indígenas Norte-Americanos/genética , Estudos de Casos e Controles , Prevalência , Fatores de Risco , Predisposição Genética para Doença , Estudos de Associação Genética , Reação em Cadeia da Polimerase em Tempo Real , Frequência do Gene , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etnologia , México/epidemiologiaRESUMO
BACKGROUND: The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico. MATERIAL AND METHODS: In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed. RESULTS: The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p < 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p > 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p < 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-platelet-ratio-index score among HCV-patients. CONCLUSION: A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.
Assuntos
Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/genética , Antivirais/efeitos adversos , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Pirofosfatases/genética , Ribavirina/efeitos adversos , Adulto , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etnologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Indígenas Norte-Americanos/genética , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Fenótipo , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Fatores de RiscoRESUMO
In Liaoning Province in northeastern China, we found a G6PD-deficient patient at the age of 3. By the classification of the World Health Organization, this patient was categorized as class I (very severe G6PD deficiency). When we investigated the G6PD gene of the patient, we found that he had a replacement of G to A at nucleotide 1339. As a result, the amino acid at position 447 should change from Gly to Arg. This replacement is known as G6PD Santiago de Cuba, because it was first discovered in a Cuban boy who showed heavy chronic anemia. Today, 28 G6PD variants have been reported in the Chinese population, and all are categorized as class II (severe deficiency) or class III (mild deficiency); in class II or III deficiency, anemia is not present in daily life, but hemolytic attack can occur when the carrier ingests certain oxidative medicines or foods. This is the first report of a G6PD-deficient Chinese patient in the category of class I. We intended to find other G6PD-deficient cases in northeastern China and tested several hundred blood samples, but no cases of G6PD deficiency were found (0/414). In central China, where falciparum malaria was endemic from the 1950s to 1970s, we found two G6PD-deficient cases (2/27) and the other members from their families whose variant type was G6PD Kaiping (1388G > T), which is a common variant in the Chinese population.
Assuntos
Povo Asiático/genética , Povo Asiático/estatística & dados numéricos , Doença de Depósito de Glicogênio Tipo I/etnologia , Doença de Depósito de Glicogênio Tipo I/genética , Anemia Hemolítica/etnologia , Anemia Hemolítica/genética , Pré-Escolar , China/epidemiologia , Saúde da Família , Inquéritos Epidemiológicos , Humanos , Masculino , Linhagem , Mutação Puntual , Índice de Gravidade de DoençaRESUMO
São descritos onze casos de anemia hemolítica em cães associados a protozoários intracitoplasmáticos em células endoteliais, diagnosticadas no Setor de Patologia Veterinária da Universidade Federal de Santa Maria, de 1985 a 2003. os animais acometidos eram machos e fêmeas, com idades que variavam de 6 meses a 10 anos. Os aspectos clínicos incluíram anorexia, apatia, vômito, emagrecimento, linfadenopatia e icterícia, presente em todos os casos. Na avaliação hematológica, realizada em seis dos onze casos, havia anemia hemofílica grave, caracterizada por intensa regeneração eritróide. Uma grande quantidade de esferócitos em quatro dos seis casos revelou uma aprovável origem imunomediada do processo. Na necropsia, os principais achados macroscópicos eram icterícia de intensidade variável, linfadenopatia, hepatomegalia e esplenomegalia. Na histologia, em todos os casos, podiam ser notados microorganismos morfologicamente compatíveis com protozoários no citoplasma de células endoteliais. Hematopoese estramedular, necrose de coagulação centrolobular no fígado e infiltrado inflamatório linfoistioplasmacitário nos órgãos parasitados eram achados freqüentes. Os dados clínicos, hematológicos, de necropsia e histopatológicos observados nos cães deste estudo sugerem que a doença trata-se uma anemia hemolítica, possivelmente de fundo auto-imune, associada a um protozoário com características morfológicas e biológicas compatíveis com Rangelia vitalli
Eleven cases of hemolytic anemia in dogs, associated with a protozoan organism present in the cytoplasm of endothelial cells are described. The cases were diagnosed at the Laboratory of Veterinary Pathology of the Universidade Federal e Santa Maria, from 1985 to 2003. Affected dogs were of both sexes and their ages ranged from 6 months to 10 years. Clinical signs included anorexia, apathy, vomiting, loos of weight, linfadenopathy, and icterus. The latter consistently in every cases. Hematological assessment carried out in six of the eleven dogs revealed severe hemolytic anemia characterized by marked erythroid regeneration. A large number of spherocytes was found in the blood smears of four of the six examined dogs; this suggested a possible immunomediated cause for the anemia. Main necropsy finds included icterus of varying degrees, enlarged lymph nodes, liver and spleen. Microscopically, in every case protozoan organisms could be observed in the cytoplasm of endothelial cells. Extramedulary hematopoeisis, centrolobular coagulative necrosis of the liver, and lymphoplasmacytic inflammatory infiltrate in the parasitized organs were frequent findings. Clinical, hematological, necropsy and histopathological findings observed in the dogs of this report suggest that the condition observed in these dogs is an hemolytic anemia, possibly of autoimmune origin and related to the presence of a protozoan with morphological and biological characteristics of Rangelia vitalii
Assuntos
Animais , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etnologia , Anemia Hemolítica/veterinária , Cães , EucariotosRESUMO
São descritos onze casos de anemia hemolítica em cães associados a protozoários intracitoplasmáticos em células endoteliais, diagnosticadas no Setor de Patologia Veterinária da Universidade Federal de Santa Maria, de 1985 a 2003. os animais acometidos eram machos e fêmeas, com idades que variavam de 6 meses a 10 anos. Os aspectos clínicos incluíram anorexia, apatia, vômito, emagrecimento, linfadenopatia e icterícia, presente em todos os casos. Na avaliação hematológica, realizada em seis dos onze casos, havia anemia hemofílica grave, caracterizada por intensa regeneração eritróide. Uma grande quantidade de esferócitos em quatro dos seis casos revelou uma aprovável origem imunomediada do processo. Na necropsia, os principais achados macroscópicos eram icterícia de intensidade variável, linfadenopatia, hepatomegalia e esplenomegalia. Na histologia, em todos os casos, podiam ser notados microorganismos morfologicamente compatíveis com protozoários no citoplasma de células endoteliais. Hematopoese estramedular, necrose de coagulação centrolobular no fígado e infiltrado inflamatório linfoistioplasmacitário nos órgãos parasitados eram achados freqüentes. Os dados clínicos, hematológicos, de necropsia e histopatológicos observados nos cães deste estudo sugerem que a doença trata-se uma anemia hemolítica, possivelmente de fundo auto-imune, associada a um protozoário com características morfológicas e biológicas compatíveis com Rangelia vitalli(AU)
Eleven cases of hemolytic anemia in dogs, associated with a protozoan organism present in the cytoplasm of endothelial cells are described. The cases were diagnosed at the Laboratory of Veterinary Pathology of the Universidade Federal e Santa Maria, from 1985 to 2003. Affected dogs were of both sexes and their ages ranged from 6 months to 10 years. Clinical signs included anorexia, apathy, vomiting, loos of weight, linfadenopathy, and icterus. The latter consistently in every cases. Hematological assessment carried out in six of the eleven dogs revealed severe hemolytic anemia characterized by marked erythroid regeneration. A large number of spherocytes was found in the blood smears of four of the six examined dogs; this suggested a possible immunomediated cause for the anemia. Main necropsy finds included icterus of varying degrees, enlarged lymph nodes, liver and spleen. Microscopically, in every case protozoan organisms could be observed in the cytoplasm of endothelial cells. Extramedulary hematopoeisis, centrolobular coagulative necrosis of the liver, and lymphoplasmacytic inflammatory infiltrate in the parasitized organs were frequent findings. Clinical, hematological, necropsy and histopathological findings observed in the dogs of this report suggest that the condition observed in these dogs is an hemolytic anemia, possibly of autoimmune origin and related to the presence of a protozoan with morphological and biological characteristics of Rangelia vitalii(AU)
Assuntos
Animais , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etnologia , Anemia Hemolítica/veterinária , Eucariotos , CãesRESUMO
Twenty-five individuals were studied from four unrelated Mexican Mestizo families with Hb D-Los Angeles. We observed five compound heterozygotes: four for Hb S and Hb D, and one for Hb D and beta-thalassemia (beta(0) 39 nonsense mutation); 16 heterozygotes: four for Hb S, seven for Hb D, and five for beta-thalassemia, while the remaining four were normal. The four Hb S/Hb D patients had severe hemolytic anemia, while in the Hb D/beta-thalassemia patient, the anemia was similar to that of a beta-thalassemia heterozygote; therefore, Hb D is clinically harmful when it is associated with Hb S. The beta(S) chromosomes were associated with the Benin haplotype in two families and Bantu in one family, while the beta(D) and beta(0) 39 mutations were associated with haplotype 1 [+ - - - - + +]. The Bantu and Benin haplotypes have been found with high frequency in Hb S individuals from the East Coast and Northwestern Mexico. The beta(D) chromosomes from Italy were also shown to be associated with haplotype 1, the most frequently observed haplotype in the world; there are no haplotype studies on beta(D) chromosomes from India or China where Hb D-Los Angeles is most common. Thus, the true origin of this mutation observed in these Mestizo families remains to be elucidated.
Assuntos
Hemoglobina Falciforme/genética , Hemoglobinas Anormais/genética , Indígenas Norte-Americanos/genética , Talassemia beta/genética , Adolescente , Idoso , Alelos , Anemia Hemolítica/etnologia , Anemia Hemolítica/genética , Criança , Pré-Escolar , Genótipo , Doenças Hematológicas/etnologia , Doenças Hematológicas/genética , Testes Hematológicos , Heterozigoto , Humanos , México/epidemiologia , MutaçãoRESUMO
This paper reports on 2 hemolytic serious reactions in 2 Arabian patients because of the use of primaquine as presumptive antimalarial treatment given in Cuba to all travellers from countries where malaria is endemic. Taking into account the non-existence of imported malaria cases in travellers from the Arab-world since more then 15 years and the frequency of individuals presenting with glucose-6-phosphate dehydrogenase deficiency it is recommended not to use this therapeutic procedure, and to maintain the rest of surveillance measures to all travellers from such region.
Assuntos
Antimaláricos/efeitos adversos , Árabes , Primaquina/efeitos adversos , Viagem , Adulto , Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/etnologia , Cuba , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/etnologia , Humanos , Malária/complicações , Malária/prevenção & controle , Masculino , Omã/etnologia , Iêmen/etnologiaRESUMO
A comparative study of 1,000 travellers coming back to Cuba from malaria-endemic areas is made. Screening for deficients of glucose 6-phosphate dehydrogenase by the methylene blue test is carried out in 500 of them; the other 500 did not undergo this test and were clinically observed throughout treatment. The figures for deficients and hemolytic syndrome were similar in the two groups. In addition the distribution according to skin color and chronology of case reporting in connection with the primaquine dose administered are analyzed. This test is useful as a screening technique in our country for prevention of hemolytic anemias through primaquine treatment.