RESUMO
UNLABELLED: The impact of IFNL3 (IL28B) polymorphism on response to interferon (IFN) treatment in patients infected with hepatitis B virus (HBV) is controversial. We aimed to investigate whether IFNL3 polymorphism (rs12979860) influences the long-term response of chronic hepatitis B (CHB) treatment to conventional IFN. DESIGN: Ninety-seven HBeAg-positive patients treated with IFN were evaluated in this study. Associations were investigated between IFNL3 genotypes and (i) HBeAg seroconversion at the end of treatment (EOT), (ii) sustained virological response (SVR) and (iii) HBsAg seroconversion through long-term follow-up (LTFU). Patients were followed for a median of 14 years. The majority of patients were infected with HBV genotype A (69.6%) and were Caucasian (77.9%). Ninety-five patients were genotyped at rs12979860. Similar IFNL3 distribution was observed among the different ethnicities (P = 0.62) or across HBV genotypes A through G (P = 0.70). Thirty-six patients experienced HBeAg seroconversion at EOT; HBeAg seroconversion rates were 37.0 and 35.5% in patients with CC and CT/TT genotypes, respectively (P = 0.82). Among the 44 patients (45%) who achieved a SVR, SVR rates were 48.9 and 39.6% in patients with CC and CT/TT IL28B genotypes, respectively (P = 0.80). HBsAg seroconversion occurred through LTFU in 28 patients. HBsAg seroconversion rates were 25.5 and 31.2% in patients with CC and CT/TT genotypes, respectively (P = 0.51). No significant relationship between IFNL3 rs12979860 and fibrosis stage was observed (P = 0.85). IFNL3 genotype was neither associated with SVR, nor with HBeAg seroconversion and long-term HBsAg seroconversion in HBeAg-positive CHB patients responding to IFN therapy.
Assuntos
Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Adulto , Idoso , DNA Viral/sangue , Feminino , Seguimentos , Genótipo , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Humanos , Interferons , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
PURPOSE: This paper describes the screening of eight patients with severe oligodontia for PAX9 and AXIN2 mutations. SUBJECTS AND METHODS: Anamnestic data and a panoramic radiograph were collected to study the phenotype of eight patients with oligodontia and their first-degree relatives. A blood sample was taken for a mutational screening for PAX9 and AXIN2 mutations. RESULTS: No mutations were discovered, but a unique nucleotide change in a conserved 5' flanking region of PAX9 was revealed. Earlier screening of the same patients for MSX1 mutations also had a negative outcome. CONCLUSIONS: Considering the discrepancy between the high incidence rate of agenesis and the relatively small number of reported causative mutations in PAX9, MSX1 and AXIN2 genes, the genetic contribution to oligodontia probably is much more heterogeneous than expected so far. Therefore negative results, like the present exclusion data, should be published more often in order to get a better appreciation of the relative contribution of these specific mutations causing oligodontia. In this context the exact number of tested probands also should be mentioned at all cases. Recent evidence of PAX9-MSX1 protein interactions in odontogenesis as well as other genes and developmental factors should receive more attention.
Assuntos
Anodontia/genética , Proteínas do Citoesqueleto/genética , Fator de Transcrição MSX1/genética , Mutação/genética , Fases de Leitura Aberta/genética , Fator de Transcrição PAX9/genética , Região 5'-Flanqueadora/genética , Adenina , Anodontia/diagnóstico por imagem , Proteína Axina , Códon/genética , Citosina , Éxons/genética , Haplótipos/genética , Humanos , Íntrons/genética , Fenótipo , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Radiografia PanorâmicaRESUMO
MSX1 mutations have been reported in four unrelated families with autosomal dominant tooth agenesis. In one family, some individuals also had cleft lip and/or palate. We have identified a novel MSX1 mutation (559 C --> T, resulting in Gln187Stop) in three individuals of one family.