RESUMO
Two new HLA-DRB3 alleles were characterized, DRB3*02:151 and DRB3*03:48.
Assuntos
Antígenos HLA-DR , Alelos , Sequência de Bases , Antígenos HLA-DR/genética , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB3/genética , HumanosAssuntos
Genômica , Antígenos HLA-C , Alelos , Antígenos HLA-C/genética , Humanos , Recombinação Genética , Análise de Sequência de DNARESUMO
Characterization of three new HLA class I alleles, B*50:73, C*08:218 and C*15:229.
Assuntos
Genes MHC Classe I , Antígenos HLA-B , Alelos , Antígenos HLA-B/genética , Antígenos HLA-C/genética , HumanosRESUMO
Identification of four new HLA-DPB1 alleles, DPB1*02:01:57, *17:01:04, *1117:01, *1124:01.
Assuntos
Alelos , Sequência de Bases , Cadeias beta de HLA-DP/genética , HumanosRESUMO
We identified a new HLA-C allele, HLA-C*03:03:01:32, with a splice site mutation in intron 5.
Assuntos
Processamento Alternativo , Antígenos HLA-C , Alelos , Genes MHC Classe I , Humanos , Íntrons/genéticaRESUMO
Four new HLA alleles characterized by NGS, B*40:455, C*03:521, C*03:04:81 and DQB1*03:431.
Assuntos
Antígenos HLA-A , Antígenos HLA-C , Alelos , Frequência do Gene , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , HumanosRESUMO
Twelve new HLA class I alleles were characterized in the Spanish population.
Assuntos
Genes MHC Classe I , Alelos , Frequência do Gene , Humanos , EspanhaRESUMO
Seven new HLA alleles were characterized by next generation sequencing in the Spanish population.
Assuntos
Antígenos HLA-A/genética , Antígeno HLA-A24/genética , Antígenos HLA-C/genética , Cadeias alfa de HLA-DQ/genética , Alelos , Estudos de Coortes , Frequência do Gene , Genética Populacional , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Polimorfismo Genético , Espanha/epidemiologiaRESUMO
A new HLA null allele, DRB1*15:176N, was characterized in a Spanish volunteer bone marrow donor.
Assuntos
Medula Óssea/química , Éxons/genética , Cadeias HLA-DRB1/genética , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Doadores de Tecidos , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Haplótipos , Humanos , Homologia de Sequência , EspanhaRESUMO
Two new HLA-C alleles, HLA-C*05:01:01:17 and -C*16:152 were detected and characterized.
Assuntos
Alelos , Antígenos HLA-C/genética , Sequência de Bases , Éxons/genética , Teste de Histocompatibilidade , HumanosRESUMO
The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populations, focusing on the most polymorphic KIR genes, which express receptors having three immunoglobulin (Ig)-like domains (KIR3DL1/S1, KIR3DL2 and KIR3DL3). We identified 13 novel alleles of KIR3DL1/S1, 13 of KIR3DL2 and 18 of KIR3DL3. Previously identified alleles, corresponding to 33 alleles of KIR3DL1/S1, 38 of KIR3DL2, and 43 of KIR3DL3, represented over 90% of the observed allele frequencies for these genes. In total we observed 37 KIR3DL1/S1 allotypes, 40 for KIR3DL2 and 44 for KIR3DL3. As KIR allotype diversity can affect NK cell function, this demonstrates potential for high functional diversity worldwide. Allelic variation further diversifies KIR haplotypes. We determined KIR3DL3â¯â¼â¯KIR3DL1/S1â¯â¼â¯KIR3DL2 haplotypes from five of the studied populations, and observed multiple population-specific haplotypes in each. This included 234 distinct haplotypes in European Americans, 191 in Ugandans, 35 in Papuans, 95 in Egyptians and 86 in Spanish populations. For another 35 populations, encompassing 642,105 individuals we focused on KIR3DL2 and identified another 375 novel alleles, with approximately half of them observed in more than one individual. The KIR allelic level data gathered from this project represents the most comprehensive summary of global KIR allelic diversity to date, and continued analysis will improve understanding of KIR allelic polymorphism in global populations. Further, the wealth of new data gathered in the course of this workshop component highlights the value of collaborative, community-based efforts in immunogenetics research, exemplified by the IHIW.
Assuntos
Antígenos HLA/genética , Imunogenética/métodos , Família Multigênica , Receptores KIR/genética , Frequência do Gene , Genética Populacional/métodos , Genótipo , Haplótipos , Humanos , Isoformas de Proteínas/genética , Análise de Sequência de DNARESUMO
Description of HLA-B*56:01:01:05S with a point mutation at the acceptor splicing site within intron 4.
Assuntos
Éxons , Antígenos HLA-B/genética , Íntrons , Mutação , Análise de Sequência de DNA/métodos , Alelos , Sequência de Bases , Humanos , Doadores de TecidosRESUMO
A new HLA-A allele, A*11:288, was characterized in a Spanish individual from the Canary Islands.
Assuntos
Antígenos HLA-A/genética , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Doadores de Tecidos , Alelos , Sequência de Aminoácidos , Humanos , Homologia de Sequência , EspanhaRESUMO
Aromatic antiepileptic drugs (AEDs) are among the drugs most frequently involved in severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS). This study investigated the associations between the genetic polymorphisms of HLA class-I and AED-induced SCARs in the Spanish population. HLA class-I genotypes were determined in AED (phenytoin[PHT],lamotrigine[LTG],carbamazepine[CBZ],phenobarbital[PB])-induced SJS/TEN (n=15) or DRESS (n=12) cases included in the Spanish SCAR registry, PIELenRed. There were 3 control groups: (A)tolerant to a single AED, (B)tolerant to any AED, and (C)Spanish population controls. For SJS/TEN, concomitant HLA-A*02:01/Cw15:02 alleles were significantly associated with PHT-cases compared to control groups B and C [(B)odds ratio(OR):14.75, p=0.009;(C)OR:27.50, p<0.001], and were close to significance with respect to control group A (p=0.060). The genotype frequency of the HLA-B*38:01 was significantly associated with PHT-LTG-cases compared with the 3 groups of controls [(A)OR:12.86, p=0.012;(B)OR:13.81; p=0.002;(C)OR:14.35, p<0.001], and with LTG-cases [(A)OR:147.00, p=0.001;(B)OR:115.00, p<0.001;(C)OR:124.70, p<0.001]. We found the HLA-B*15:02 allele in a Spanish Romani patient with a CBZ-case. The HLA-A*11:01 was significantly associated with CBZ-cases [(A)OR:63.89, p=0.002;(B)OR:36.33, p=0.005;(C)OR:28.29, p=0.007]. For DRESS, the HLA-A*24:02 genotype frequency was statistically significant in the PHT-LTG-cases [(A)OR:22.56, p=0.003;(B)OR:23.50. p=0.001; (C)OR:33.25, p<0.001], and in the LTG-cases [(A),OR:49.00, p=0.015;(B)OR:27.77, p=0.005; (C)OR:34.53, p=0.002]. HLA-A*31:01 was significantly associated with the CBZ-cases [(A)OR:22.00, p=0.047;(B)OR:29.50, p=0.033;(C)OR:35.14, p=0.006]. In conclusion, we identified several significant genetic risk factors for the first time in the Spanish Caucasian population: HLA-A*02:01/Cw*15:02 combination as a risk factor for PHT-induced SJS/TEN, HLA-B*38:01 for LTG- and PHT- induced SJS/TEN, HLA-A*11:01 for CBZ-induced SJS/TEN, and HLA-A*24:02 for LTG- and PHT- induced DRESS. The strong association between HLA*31:01 and CBZ-DRESS in Europeans was confirmed in this study.
Assuntos
Anticonvulsivantes/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/genética , Genes MHC Classe I/genética , Predisposição Genética para Doença/genética , Síndrome de Stevens-Johnson/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Espanha , Síndrome de Stevens-Johnson/etiologia , População Branca/genética , Adulto JovemRESUMO
The HLA-B*15:02 allele is a risk factor for carbamazepine (CBZ)-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in populations where the allele is prevalent. Han Chinese and Thai patients are advised to take a genetic test before introducing CBZ. Such testing is not recommended for patients of European descent. We report the case of a Spanish Romani patient who developed Stevens-Johnson syndrome upon treatment with CBZ. In vitro assays confirmed CBZ as the culprit drug. HLA typing showed that the patient carried the HLA-B*15:02 allele. A public database search revealed that 2% of Spanish Romani people likely carry the risk variant HLA-B*15:02 and therefore may be included in the population to be tested prior to beginning treatment with CBZ.
