RESUMEN
Whilst immune-mediated adverse drug reactions (ADRs) are rare, they are potentially life-threatening and present a major problem for clinicians. The underlying mechanisms that cause ADRs are not fully understood although genomewide association studies (GWAS) and case-control investigations have associated human leucocyte antigen (HLA) alleles as risk factors. There is evidence that a patient's ethnic background can have an impact on their risk of developing an ADR. This review summarizes the evidence related to HLA alleles and ADRs with particular focus on patient ethnicity. Our analysis indicated that many of the alleles which have been associated with ADRs are found at higher frequencies in Asian populations. The data also showed that many of the alleles that are reported to be statistically significantly associated with ADRs are in linkage disequilibrium with each other and that they form haplotypes specific to certain ethnicities indicating at least some of the allele associations may not be causal.
Asunto(s)
Antibacterianos/efectos adversos , Anticonvulsivantes/efectos adversos , Infecciones Bacterianas/etnología , Epilepsia/etnología , Supresores de la Gota/efectos adversos , Antígenos HLA/inmunología , Enfermedades Reumáticas/etnología , Alelos , Antibacterianos/administración & dosificación , Anticonvulsivantes/administración & dosificación , Pueblo Asiatico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/genética , Infecciones Bacterianas/inmunología , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Epilepsia/inmunología , Etnicidad , Regulación de la Expresión Génica/inmunología , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Supresores de la Gota/administración & dosificación , Antígenos HLA/genética , Haplotipos , Humanos , Desequilibrio de Ligamiento , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/genética , Enfermedades Reumáticas/inmunología , Insuficiencia del TratamientoRESUMEN
In this study, we report an approach to characterize individual BoLA haplotypes using cells from parthenogenetic bovine embryos derived from slaughterhouse ovaries. Eight of the 15 parthenogenetic embryos so obtained had not undergone meiotic recombination on the BoLA region and were suitable to describe BoLA haplotypes. Detailed analysis of the BoLA class IIa region identified seven different class IIa haplotypes, including six not previously described and two new alleles of BoLA-DQA and one BoLA-DQB. Our method provided reliable sources of homozygous DNA to describe BoLA haplotypes.
Asunto(s)
Bovinos/genética , Genes MHC Clase II , Haplotipos , Alelos , Animales , Embrión de Mamíferos , PartenogénesisRESUMEN
In this study, we sought to investigate the genetic influence of two HLA-G 3'-untranslated region (3'-UTR) polymorphisms - 14 bp (rs66554220) and +3142C>G (rs1063320) and their compounding haplotypes in susceptibility to rheumatoid arthritis (RA) in a two-region Brazilian study comprising of 539 patients and 489 controls. All subjects were polymerase chain reaction (PCR) genotyped for the referred polymorphisms and logistic regression models controlling for sex, city and age were performed. Homozygozity for the +3142G allele was associated with an increased risk of RA [odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.075-1.959, P(Bonf) = 0.030], whereas no association was observed for the 14 bp polymorphism. Haplotype comparisons between patients and controls showed a decreased frequency of the delC haplotype in patients (OR = 0.70, 95% CI = 0.521-0.946, P(Bonf) = 0.040), which remained significant in the rheumatoid factor (RF)-positive group (OR = 0.66, 95% CI = 0.482-0.900, P(Bonf) = 0.018), but not in the RF-negative group. These results corroborate the hypothesis of an involvement of HLA-G in the susceptibility of RA. The +3142G allele is associated with haplotype lineages that share high identity and are regarded as low producers. The presence of the G allele in homozygosis could be responsible for a low HLA-G expression profile that could favor the triggering of RA.
Asunto(s)
Regiones no Traducidas 3' , Alelos , Artritis Reumatoide/genética , Frecuencia de los Genes , Antígenos HLA-G/genética , Polimorfismo Genético , Adulto , Anciano , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
Systemic lupus erythematosus (SLE) is an autoimmune disorder of the connective tissue with a wide and heterogeneous spectrum of manifestations, with renal and neurological involvement usually related to worse prognosis. SLE more frequently affects females of reproductive age, and a high prevalence and renal manifestation seem to be associated with non-European ethnicity. The present study aims to investigate candidate loci to SLE predisposition and evaluate the influence of ethnic ancestry in the disease risk and clinical phenotypic heterogeneity of lupus at onset. Samples represented by 111 patients and 345 controls, originated from the city of Belém, located in the Northern Region of Brazil, were investigated for polymorphisms in HLA-G, HLA-C, SLC11A1, MTHFR, CASP8 and 15 KIR genes, in addition to 89 Amerindian samples genotyped for SLC11A1. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. Predisposition to SLE was associated with GTGT deletion at the SLC11A1 3'UTR, presence of KIR2DS2 +/KIR2DS5 +/KIR3DS1 + profile, increased number of stimulatory KIR genes, and European and Amerindian ancestries. The ancestry analysis ruled out ethnic differences between controls and patients as the source of the observed associations. Moreover, the African ancestry was associated with renal manifestations.
Asunto(s)
Proteínas de Transporte de Catión/genética , Etnicidad/genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Lupus Eritematoso Sistémico/genética , Polimorfismo Genético , Receptores KIR/genética , Adulto , Edad de Inicio , Brasil , Ciudades , Femenino , Frecuencia de los Genes , Humanos , Lupus Eritematoso Sistémico/etnología , Masculino , Receptores KIR3DS1/genéticaRESUMEN
The aim of the present study was the development of a multiplex genotyping panel of eight microsatellite markers of Arapaima gigas, previously described. Specific primer pairs were developed, each one of them marked with either FAM-6, HEX or NED. The amplification conditions using the new primers were standardized for a single reaction. The results obtained demonstrate high heterozygosity (average of 0.69) in a Lower Amazon population. The multiplex system described can thus be considered a fast, efficient and inexpensive method for the investigation of genetic variability in Arapaima populations.
Asunto(s)
Peces/genética , Variación Genética , Repeticiones de Microsatélite/genética , Reacción en Cadena de la Polimerasa/economía , Reacción en Cadena de la Polimerasa/métodos , Alelos , Animales , Brasil , Cartilla de ADN/química , Marcadores Genéticos , Genotipo , Heterocigoto , Polimorfismo Genético , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
The aim of the present study was the development of a multiplex genotyping panel of eight microsatellite markers of Arapaima gigas, previously described. Specific primer pairs were developed, each one of them marked with either FAM-6, HEX or NED. The amplification conditions using the new primers were standardized for a single reaction. The results obtained demonstrate high heterozygosity (average of 0.69) in a Lower Amazon population. The multiplex system described can thus be considered a fast, efficient and inexpensive method for the investigation of genetic variability in Arapaima populations.