A nationwide hepatitis B virus (HBV) vaccination program was implemented in China starting in 1992.To study the change in HBV variant prevalence with massive immunization, large HBV surface protein (LHBs) genes from HBV surface antigen (HBsAg)-positive sera were amplified and sequenced. The prevalences of LHBs mutants were compared between the 1992 and 2005 surveys in child and adult groups. The prevalence of "␣" determinant mutants in the children increased from 6.5% in 1992 to 14.8% in 2005, where the G145R mutant occurred most frequently. In contrast, mutation frequencies showed little difference between 1992 (9.4%) and 2005 (9.9%) in adults. Moreover, compared to the 1992 survey, the child group surface (S) protein mutation frequency specifically increased (P ؍ 0.005) in the 2005 survey, but the pre-S region mutation frequency did not show a significant difference (P > 0.05). However, the mutation frequency in the adult group increased in both the pre-S and S regions. Furthermore, the frequencies of the disease-related pre-S2 deletion and start codon mutations were significantly higher in the adult groups than in the child groups in both the 1992 and 2005 surveys (P < 0.01). Massive immunization enhances the HBV S protein mutation; the prevalence of LHBs mutants, particularly disease-related mutants, tends to increase with patient age. Hepatitis B virus (HBV) infection is a serious public health problem worldwide and a major cause of hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) (1). An estimated 350 million people are living with chronic hepatitis B worldwide (2). In China, a national serosurvey in 1992 revealed that the prevalence of hepatitis B surface antigen (HBsAg) was 9.8% in the general population (3). The most recent national serosurvey, in 2006, demonstrated that the HBsAg carrier rate is 7.2%, and the number of chronic HBV carriers is estimated to be 9.3 million (3, 4).China began infant vaccine injections in national disease surveillance points (DSP) as early as 1986, and the four provinces in the current study were also to perform infant vaccinations at that time (5). In 1992, China formally recommended routine immunization with the hepatitis B virus vaccine for infants. Since then, the massive vaccination program has effectively decreased the risk of HBV infection, and the rate of HBsAg-positive children has significantly declined. Among children Ͻ5 years of age, the prevalence of HBsAg has dramatically decreased from 9.67% (1992) to 0.96% (2006). It is estimated that 80 million children are free from HBV infection due to the vaccination program (3).While universal infantile HBV vaccination is very efficacious, an increase in the mutant prevalence or "vaccine escape mutation" after immunization posed a potential threat to the long-term success of massive vaccination (6-8). Hsu et al. studied the prevalence of HBV variants in children in Taiwan and demonstrated that universal vaccination had accelerated the accumulation of HBsAg "␣" determinant mutants (9). The ␣ determinant is a co...
Substantial differences in the outcome of childhood CP with different tumour growth patterns and locations were found, which suggested that diverse therapeutic considerations, especially endocrinological substitution, might be emphasized.
Background: Noise-induced hearing loss (NIHL) is a complex disease induced by a combination of genetic and environmental factors. Paraoxonase2 (PON2) gene involved in the regulation of reactive oxygen species, and affecting the vulnerability of cochlea to NIHL, and ATPase, calcium-transporting, plasma membrane 2 (ATP2B2) gene which encodes plasma membrane calcium-transporting ATPase isoform 2 (PMCA2) are the candidate genes relating to the attack of NIHL. In this study, we investigated whether ATP2B2 and PON2 polymorphisms were associated with NIHL in Chinese of Han nationality population. Methods: We performed a case-control study between six single nucleotide polymorphisms (SNPs) (rs1719571, rs3209637 and rs4327369 within ATP2B2, rs12026, rs7785846 and rs12704796 within PON2) and NIHL in 454 subjects. All the SNPs were genotypes, using the TaqMan MGB probe assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs) with logistic regression analysis to test the level of association for SNPs. Results: In our study, 221 subjects with hearing loss and 233 subjects without hearing loss were recruited.The frequencies of the CG and CG + GG genotype of rs12026 (PON2) conferred risk factors for NIHL with adjusted OR values of 2.62 (95% CI, 1.69-4.06) and 2.48 (95% CI, 1.63-3.78), respectively. This kind of significance was also found at locus rs7785846, where genotypes CT and CT + TT were the risk types, with adjusted ORs of 2.52 (95% CI, 1.62-3.93) and 2.35 (95% CI, 1.54-3.58), respectively. We performed stratified analysis per noise exposure level, when it came to rs7785846 and rs12026 in the >92 dB(A) noise exposure group, the subjects who carried heterozygote were of significantly (P<0.01) higher susceptibility to NIHL than homozygote carriers. By contrast, no significantly higher risk was found for any rs12704796 genotypes or any genotypes in ATP2B2 (P>0.05), which may suggest that these SNPs did not have significant effects on noise susceptibility across noise exposure. Conclusions: Our research suggested that PON2 might play a role in the etiology of NIHL in Chinese of Han nationality population.
BackgroundThe efficacy of direct-acting antiviral agents (DAAs) could be attenuated by the presence of resistance-associated variants (RAVs). The aim of this study was to investigate the natural prevalence of RAVs among Chinese HCV genotype 1b patients and analyze the efficacy of pegylated interferon (PegIFN)/ribavirin (RBV) therapy in patients with and without RAVs at baseline.MethodsDirect sequencing of the HCV NS3, NS5A and NS5B regions was performed in baseline serum samples of 117 DAAs-naïve subjects infected with HCV genotype 1b. The efficacy of PegIFN/RBV therapy in patients with and without RAVs at baseline was analyzed by comparing the response rates between patients with RAVs and patients with wild type virus.ResultsThe incidence of RAVs was 8.00% (8/100) in the NS3 region (T54S, n = 1, 1.00%; R117H, n = 5, 5.00%; S122T, n = 1, 1.00%; S174F, n = 1, 1.00%), 29.91% (32/107) in the NS5A region (L28M, n = 12, 11.21%; R30Q, n = 10, 9.35%; L31M, n = 1, 0.93%; P58S, n = 4, 3.74%; Y93H, n = 8, 7.48%) and 98.15% (106/108) in the NS5B region (L159F, n = 1, 0.93%; C316N, n = 103, 95.37%; A421V, n = 6, 5.56%). The response rates to PegIFN/RBV treatment did not differ between patients with or without RAVs in the NS5A region.ConclusionsPre-existing RAVs, including key RAVs, were detected in Chinese DAAs-naïve patients infected with HCV genotype 1b. IFN-based therapy could be a good option for patients with RAVs, especially key RAVs, at baseline.
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