RESUMO
Aims: To determine genetic susceptibility markers for carbamazepine (CBZ) and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese. Methods: A case-control study was performed involving 122 patients with CBZ or allopurinol-induced SCARs and 120 drug tolerant controls. Results:HLA-B*58:01 was strongly associated with allopurinol-induced SCARs and strongly correlated with SNP rs9263726. HLA-B*15:02 was associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis but not with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms. No association was found between HLA-A*31:01 and CBZ-induced SCARs. HLA-B*58:01 and rs3909184 allele A with renal insufficiency were shown to increase the risk of allopurinol-induced SCARs. Conclusion:HLA-B*58:01 and HLA-B*15:02 confer susceptibility to allopurinol-induced SCARs and CBZ-induced SJS/TEN in Vietnamese. SNP rs9263726 can be used as a surrogate marker in identifying HLA-B*58:01.
Assuntos
Alopurinol/efeitos adversos , Povo Asiático/genética , Carbamazepina/efeitos adversos , Predisposição Genética para Doença/genética , Antígenos HLA-B/genética , Síndrome de Stevens-Johnson/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/efeitos adversos , Estudos de Casos e Controles , Feminino , Previsões , Predisposição Genética para Doença/epidemiologia , Supressores da Gota/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/epidemiologia , Vietnã/epidemiologia , Adulto JovemRESUMO
Aim: To examine gene expression in different clinical phenotypes of allopurinol-induced severe cutaneous adverse reactions (SCARs). Materials & methods: Gene expression profiling was performed using microarray on 11 RNA samples (four controls, three hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms, four Stevens-Johnson syndrome/toxic epidermal necrolysis) followed by quantitative real-time PCR in a total of 11 SCARs patients and 11 controls. Results: The biological pathways which were significantly enriched in differentially expressed genes in Stevens-Johnson syndrome/toxic epidermal necrolysis compared with hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms patients included; cell surface interactions at the vascular wall, immunoregulatory interactions at the immunological synapse and MyD88 signaling pathways. Overexpression of miR146a occurred in allopurinol-tolerant HLA-B*58:01 carriers. Conclusion: Biological pathways are identified which appear to be implicated in determining clinical phenotypes in allopurinol-induced SCARs. Overexpression of miR146a is potentially important for allopurinol tolerance in HLA-B*58:01 carriers.
Assuntos
Alopurinol/efeitos adversos , Povo Asiático/genética , Toxidermias/genética , Expressão Gênica/genética , Pele/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/efeitos adversos , Exantema/induzido quimicamente , Exantema/genética , Feminino , Perfilação da Expressão Gênica/métodos , Supressores da Gota/efeitos adversos , Antígenos HLA-B/genética , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/genética , Síndrome de Stevens-Johnson/genéticaRESUMO
BACKGROUND: Although Vietnam is a region with a plant-based diet that has a high zinc deficiency, epidemiological data showing how this affects pregnant women are limited. This study explores the prevalence of zinc deficiency and possible correlates in pregnant Vietnamese women in Ho Chi Minh City. METHODS: This was a cross-sectional study conducted at a general hospital in Ho Chi Minh City, Vietnam. All pregnant women who came to their first antenatal care visit from November 2011 to June 2012 were recruited. Those taking a vitamin and/or mineral supplement were excluded. Serum zinc concentrations, determined by a standard colorimetric method, of 10.7 µmol/L-17.5 µmol/L (70.0 g/dL-114 g/dL) were classified as normal and under 10.7 µmol/L (70.0 g/dL) as zinc deficient. RESULTS: In total, 254 pregnant women were invited and 107 (42%) participated. The mean age of participants was 29 years, and mean gestational age was 10 weeks. Median zinc concentration in serum was 13.6 µmol/L, and the prevalence of zinc deficiency was 29% (95% CI=21%-39%). The daily intake of a milk product supplement was the only significant correlate of zinc deficiency of the items investigated (adjusted OR=0.40, 95% CI=0.16-0.99, p=0.049). DISCUSSION: This is the first study reporting that more than 25% of pregnant Vietnamese women in Ho Chi Minh City are zinc deficient. Further academic and clinical input is needed to confirm the scale of this neglected issue and to investigate the potential of milk product supplementation in this population.