RESUMO
The present study was undertaken to investigate genetic variations present in the coding regions of the UGT1A1 gene among the Gilbert's syndrome patients. Analysis of genetic variations was performed by direct DNA sequencing among the patients that do not have any polymorphic variations in the promoter regions of the UGT1A1 gene. We identified seven different sequence variations among Gilbert's Syndrome patients, of which four were novel. Out of seven variants, six missense and one silent single nucleotide substitutions were present in the UGT1A1 gene. In addition, molecular modeling of UGT1A1 (H55R, P152S and N212H) variants suggested a reduced activity of the enzyme. This study demonstrates that different variations present in the UGT1A1 gene and specifically, the H55R variation had a significant effect on bilirubin levels and could be genetic risk factors for hyperbilirubinemia.
Assuntos
Doença de Gilbert/genética , Glucuronosiltransferase/genética , Adulto , Bilirrubina/sangue , Bilirrubina/genética , Feminino , Variação Genética/genética , Genótipo , Doença de Gilbert/fisiopatologia , Glucuronosiltransferase/fisiologia , Humanos , Hiperbilirrubinemia/genética , Índia , Masculino , Mutação , Regiões Promotoras Genéticas/genéticaRESUMO
OBJECTIVE: The present study was undertaken to investigate the genotype and allele frequencies of the variants in the four bilirubin metabolism genes (UGT1A1, OATP2, HMOX1, and BLVRA) and their association with hyperbilirubinemia. MATERIAL AND METHODS: Genotyping of 17 genetic variants was performed in 115 adults with hyperbilirubinemia and 150 controls by PCR-RFLP, GeneScan analysis, and direct DNA sequencing. RESULTS: Genetic polymorphisms of the UGT1A1 promoter, specifically the T-3279G phenobarbital-responsive enhancer module and (TA)7 dinucleotide repeat, as well as the intron and coding region variants of the OATP2, HMOX1, and BLVRA genes, were significantly higher among the cases than the controls. Further, nearly 82% of the cases showed the presence of significantly four or more variants as compared to 37% of the controls (P < 0.0001) and the mean total serum bilirubin levels also increased according to the number of variants co-expressed. CONCLUSIONS: This study demonstrates that polymorphisms in the bilirubin metabolism genes had a significant effect on bilirubin levels and could be genetic risk factors for hyperbilirubinemia.
Assuntos
Doença de Gilbert/genética , Glucuronosiltransferase/genética , Heme Oxigenase-1/genética , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Polimorfismo Genético , Regiões Promotoras Genéticas , Adulto JovemRESUMO
HLA-B*15:679 and HLA-C*15:02:01:61 differ from HLA-B*15:12:01 and HLA-C*15:02:01:01 by a single nucleotides.
Assuntos
Alelos , Sequência de Bases , Antígenos HLA-C , Teste de Histocompatibilidade , Humanos , Antígenos HLA-C/genética , Índia , Éxons , Análise de Sequência de DNA/métodos , Polimorfismo de Nucleotídeo Único , Antígeno HLA-B15/genética , Antígeno HLA-B15/imunologia , Alinhamento de Sequência , CódonRESUMO
Allele variants HLA-C*01:02:01:74Q and -C*15:02:01:63 differ from -C*01:02:01:01 and -15:02:01:01 by a single nucleotide, respectively.
Assuntos
Alelos , Antígenos HLA-C , Teste de Histocompatibilidade , Humanos , Antígenos HLA-C/genética , Polimorfismo de Nucleotídeo Único , Éxons , Índia , Sequência de Bases , Análise de Sequência de DNA/métodosRESUMO
Acute Myeloid Leukemia (AML) is a complex disease with rapid progression and poor/unsatisfactory outcomes. In the past few years, the focus has been on developing newer therapies for AML; however, relapse remains a significant problem. Natural Killer cells have strong anti-tumor potential against AML. This NK-mediated cytotoxicity is often restricted by cellular defects caused by disease-associated mechanisms, which can lead to disease progression. A stark feature of AML is the low/no expression of the cognate HLA ligands for the activating KIR receptors, due to which these tumor cells evade NK-mediated lysis. Recently, different Natural Killer cell therapies have been implicated in treating AML, such as the adoptive NK cell transfer, Chimeric antigen receptor-modified NK (CAR-NK) cell therapy, antibodies, cytokine, and drug treatment. However, the data available is scarce, and the outcomes vary between different transplant settings and different types of leukemia. Moreover, remission achieved by some of these therapies is only for a short time. In this mini-review, we will discuss the role of NK cell defects in AML progression, particularly the expression of different cell surface markers, the available NK cell therapies, and the results from various preclinical and clinical trials.
Assuntos
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/patologia , Células Matadoras Naturais , Imunoterapia Adotiva/métodos , Receptores KIR/metabolismo , Citocinas/metabolismoRESUMO
The novel HLA-B*15:665 and HLA-C*12:02:02:23 alleles were detected during the routine HLA typing process.
RESUMO
Novel HLA-C*06:02:01:94 and -C*15:02:01:58 alleles were detected during the routine HLA typing process.
RESUMO
The novel HLA-B*58:01:01:19 allele was characterized using next generation sequencing technology.
Assuntos
Genes MHC Classe I , Antígenos HLA-B , Humanos , Alelos , Antígenos HLA-B/genética , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
The novel allele HLA-C*07:02:01:184 as compared with HLA-C*07:02:01:03 displays polymorphism at position; gDNA 2896 (G > C).
Assuntos
Antígenos HLA-C , Humanos , Alelos , Sequência de Bases , Genes MHC Classe I , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos HLA-C/genéticaRESUMO
The novel allele HLA-A*11:01:01:86 differs from HLA-A*11:01:01:86 by one nucleotide change at position; gDNA-32 (A- > C).
Assuntos
Antígenos HLA-A , Nucleotídeos , Humanos , Alelos , Índia , Antígenos HLA-A/genética , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
The novel HLA-C*12:02:47 allele was detected during routine HLA typing.
Assuntos
Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , ÍndiaRESUMO
The novel allele HLA-C*06:02:38:02 differs from HLA-C*06:02:38:01 by a nucleotide change at position; gDNA 168 T â A.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Índia , NucleotídeosRESUMO
The novel alleles HLA-DQA1*01:01:01:11 and -DQA1*01:03:01:13 were detected during the routine HLA typing process.
Assuntos
Alelos , Humanos , Cadeias alfa de HLA-DQ/genética , Índia , Teste de Histocompatibilidade , Análise de Sequência de DNARESUMO
The novel HLA-DPA1*01:03:01:64 allele was detected during routine HLA typing.
Assuntos
Cadeias alfa de HLA-DP , Humanos , Alelos , Cadeias alfa de HLA-DP/genética , Teste de Histocompatibilidade , ÍndiaRESUMO
The novel HLA-DQA1*01:01:01:10 allele differs from HLA-DQA1*01:01:01:07 by a single nucleotide change at gDNA 702 G T.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Análise de Sequência de DNA , Cadeias alfa de HLA-DQ/genética , ÍndiaRESUMO
HLA-C*07:04:01:19 differs from C*07:04:01:01 by one nucleotide change in gDNA at position 2420 in intron 5.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Índia , ÍntronsRESUMO
The novel HLA-B*40:01:02:59 and HLA-C*05:01:73 alleles were detected during the routine HLA typing process.