Mutations located in the 109-amino acid fragment of NS5B are typically associated with resistance to interferon (IFN) and ribavirin (RIB) and to new antiviral drugs. The prevalence of these mutations was examined in 69 drug-naïve individuals with hepatitis C virus (HCV) infections in Rio de Janeiro, Brazil. Mutations related to non-response to IFN/RIB were observed in all subtypes studied (1a, 1b, 2b, 3a and 4). The most common mutation was Q309R, present in all subtypes, except subtype 2b with frequency above 20%. D244N was detected only in subtype 3a and A333E was detected only in subtype 2b. We did not detect the S282T, S326G or T329I mutations in any of the samples analysed. Of note, the C316N mutation, previously related to a new non-nucleoside compound (HCV796 and AG-021541), was observed in only eight of 33 (24%) samples from subtype 1b. Site 316 was under positive selection in this HCV variant. Our data highlight the presence of previously described resistance mutations in HCV genotypes from drug-naïve patients.

Os alelos HLA-DRB1, que codificam uma sequência de aminoácidos (QKRAA/QRRAA/RRRAA) nas posições 70 a 74 da terceira região hipervariável da cadeia β1 do gene DRB1, denominada epítopo compartilhado (EC), estão associados a maior suscetibilidade e gravidade para artrite reumatoide (AR) em diversas populações. OBJETIVO: Determinar a frequência dos alelos HLA-DRB1 em pacientes brasileiros com AR, e sua associação a fator reumatoide (FR) e anticorpos antipeptídeos citrulinados (ACPA). MATERIAL E MÉTODOS: Foram incluídos 412 pacientes com AR e 215 controles. A tipificação HLA-DRB1 foi realizada pela reação em cadeia da polimerase (PCR) usando primers específicos e hibridização com oligonucleotídeos de sequência específica (SSOP). A pesquisa de ACPA foi determinada pela técnica de ELISA, e a do FR por nefelometria. Para análises estatísticas foram utilizados os testes do qui-quadrado e t de Student e a regressão logística. RESULTADOS: Alelos HLA-DRB1*04:01, *04:04 e *04:05 associaram-se à AR (P < 0,05)); a despeito do amplo intervalo de confiança, vale a pena ressaltar a associação observada entre o alelo DRB1*09:01 e a doença (P < 0,05). Alelos HLA-DRB1 EC+ foram observados em 62,8% dos pacientes e em 31,1% do grupo-controle (OR 3,62; P < 0,001) e estiveram associados a ACPA (OR 2,03; P < 0,001). Alelos DRB1-DERAA mostraram efeito protetor para AR (OR 0,42; P < 0,001). CONCLUSÃO: Em uma amostra de pacientes brasileiros com AR de etnia majoritariamente mestiça, alelos HLA-DRB1 EC+ estiveram associados à suscetibilidade à doença e à presença de ACPA.

The HLA-DRB1 alleles encoding an amino acid sequence (QKRAA/QRRAA/RRRAA) at position 70 74 of the third hypervariable region of the β1 chain of the HLA-DRB1 gene, called shared epitope (SE), are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in different populations. OBJECTIVE: To determine the frequency of HLA-DRB1 alleles in Brazilian patients with RA and their association with rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA). METHODS: Four hundred and twelve patients with RA (ACR 1987) and 215 controls were included. HLA-DRB1 typing was performed by use of polymerase chain reaction (PCR) with specific primers and hybridization with sequence-specific oligonucleotide probe (SSOP). ACPA was measured by use of the ELISA technique and RF by nephelometry. The statistical analysis comprised the chi-square and Student t tests and logistic regression. RESULTS: HLA-DRB1*04:01, *04:04, *04:05 alleles were associated with RA (P < 0.05); despite the wide confidence interval, it is worth noting the association between the DRB1*09:01 allele and RA (P < 0.05). HLA-DRB1 SE+ alleles were observed in 62.8% of the patients and in 31.1% of controls (OR 3.62; P < 0.001) and were associated with ACPA (OR 2.03; P < 0.001). DRB1-DERAA alleles showed a protective effect against RA (OR 0.42; P < 0.001). CONCLUSION: In a sample of Brazilian patients with RA, most of whom of mixed heritage, HLA-DRB1 SE+ alleles were associated with susceptibility to disease and presence of ACPA.