Publications (158) View all
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Article: A Functional Polymorphism at the FGF10 Gene Is Associated with Extreme Myopia.
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ABSTRACT: PURPOSE: Fibroblast growth factor-10 (FGF10) can modulate extracellular matrix associated genes and therefore it could be a myopia susceptibility gene. This study used an animal model, single nucleotide polymorphisms (SNPs) association and genetic functional assay to evaluate FGF10 gene for myopia. METHODS: The expression levels of FGF10 gene were compared among the form deprivation myopic (FDM) eyes, the fellow eyes of the FDM group and the normal eyes of experimental mice. In the present study 1,020 cases (≤-6.0 D) and 960 controls (≥-1.5 D) were enrolled from a Chinese population. Eight tagging SNPs were genotyped to test for an association between genotypes and myopia. The luciferase reporter assay was conducted for the particular SNP to assess the allelic effect on gene expression. RESULTS: The sclera of FDM eyes had a 2.57-fold higher level of FGF10 mRNA (p=0.018) than the fellow eyes. Although no SNP was associated with high myopia, SNP rs339501 was significantly associated with extreme myopia (≤-10D, p=0.008) and the OR was 1.58 for G allele carriers. The luciferase assay showed that the risk G allele significantly caused a higher expression level than the A allele (P = 0.011). CONCLUSIONS: The evidence suggested FGF10 to be a risk factor for myopia. The sclera of myopic eyes had higher FGF10 levels. The risk G allele of SNP rs339501 was associated with extreme myopia in human and caused a higher gene expression in the luciferase assay. It is concluded that the FGF10 could have been involved in the development of myopia.Investigative ophthalmology & visual science 04/2013; · 3.43 Impact Factor -
Article: Clinical utility of host genetic IL-28B variants in hepatitis C virus genotype 1 Asian patients retreated with pegylated interferon plus ribavirin.
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ABSTRACT: BACKGROUND AND AIM: Host interleukin-28B (IL-28B) genetic variants determine a sustained virological responsese (SVR) in hepatitis C virus genotype 1 (HCV-1) treatment-naïve patients. Its impact on treatment-experienced Asian patients with peginterferon/ribavirin in is to be elucidated. METHODS: IL-28B rs8099917 genotype was determined in 70 HCV-1 treatment-experienced patients retreated with 48-week peginterferon/ribavirin. RESULTS: The SVR rate was 60.0% and was significantly higher in previous relapsers than in non-responders (72.7% and 13.3%, P<0.001). Multivariate analysis revealed that the most important factor predictive of an SVR was previous relapse (Odds ratio [OR]/95% C.I.: 14.76/2.72-80.06, P=0.002), followed by the carriage of rs8099917 TT genotype (OR/ 95% C.I.: 7.67/1.27-46.49, P=0.03). Comparing to patients with TG/GG genotype, those with TT genotype had significantly higher rates of rapid virological response (29.3% vs. 0%, P=0.03), end-of-treatment virological response (86.2% vs. 50.0%, P=0.01), SVR (69.0% vs. 16.7%, P=0.002) and lower relapse rate (22.0 % vs. 66.7%, P=0.04). The SVR rate was similarly low between previous non-responders with different rs8099917 genotypes (12.5% vs. 14.3%, P=1). On the contrary, previous relapsers with rs8099917 TT genotype had a significantly higher SVR rate than those who carried rs8099917 TG/GG genotype (78.0 % vs. 20.0%, P=0.02). Stepwise logistic regression analysis revealed that the only factor predictive of an SVR in previous relapsers was the carriage of rs809997 TT genotype (OR/ 95% CI:18.50/1.82-188.39, P=0.014). CONCLUSIONS: Host IL-28B genetic variants played a role in Asian relapsers but not non-responders retreated with peginterferon/ribavirin. Direct antiviral agents might be possibly avoidable in Asian relapsers with favorable IL-28B genotype.Journal of Gastroenterology and Hepatology 04/2013; · 2.87 Impact Factor -
Article: Glucose abnormalities in hepatitis C virus infection.
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ABSTRACT: Hepatitis C virus (HCV) infection is one of the most important causes of cirrhosis and hepatocellular carcinoma and has a tremendous impact on public health worldwide. HCV is both hepatotropic and lymphotropic. Replication of HCV in diseased extrahepatic organs and tissues may either trigger latent autoimmunity or induce autoimmune disorders. In addition to established liver injury, type 2 diabetes mellitus (T2DM) is an important feature of extrahepatic metabolic disorders which is attributed to HCV infection. It also has some impact on the disease activity, disease course, clinical outcomes, and treatment efficacy of antiviral therapy. Previous experimental and clinical findings have highly suggested that HCV per se is diabetogenic. The cause-effect interaction between a common endocrine disorder and an infectious disease is an important issue to elucidate. Although the precise mechanisms whereby HCV infection leads to insulin resistance (IR) and glucose abnormalities are not entirely clear, it differs from the usual pathogenesis of T2DM in those with non-HCV liver diseases. This review initially highlights epidemiological and pathophysiological studies addressing the mutual link between chronic HCV infection (CHC) and T2DM. The characteristics of glucose abnormalities in this special population are depicted from the current evidence. The mutual roles of IR and CHC with respect to the prediction of treatment efficacy, how treatment response affects IR, and the role of pancreatic beta cell function in the entire suite are discussed. With the rapid progression of antiviral therapy for CHC in the past decade, we have also listed some points of future perspective in this issue.The Kaohsiung journal of medical sciences 02/2013; 29(2):61-8. · 0.61 Impact Factor -
Article: Sustained hcv clearance and increased HBsAg seroclearance in patients with dual chronic hepatitis C and B during post-treatment follow-up.
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ABSTRACT: Patients dually infected with hepatitis C virus (HCV)/hepatitis B virus (HBV) have a higher risk of developing advanced liver disease or hepatocellular carcinoma compared to monoinfected patients. Our previous study showed a similar rate of sustained virologic response (SVR) after peginterferon alfa-2a and ribavirin combination therapy in these patients compared to HCV monoinfected patients, and a high hepatitis B surface antigen (HBsAg) seroclearance rate. The durability of hepatitis C and B clearance in dually infected patients was investigated by a 5-year follow-up study. Patients with active HCV genotype 1, both HBV coinfected (n=97) and monoinfected (n=110), received a 48-week combination therapy with peginterferon alfa-2a plus ribavirin. Patients with active HCV genotype 2/3, both HBV coinfected (n=64) and monoinfected (n=50) patients received a 24-week combination therapy. A total of 295 (91.9%) patients completed treatment and 24 weeks post-treatment follow-up; 264 (89.5%) agreed to receive additional follow-up for up to 5 years after the end of treatment. After a median follow-up of 4.6 + 1.0 years, 6 of the 232 patients achieving SVR developed HCV RNA reappearance, including 5 HCV genotype 1/HBV coinfected patients and 1 HCV genotype 2/3 monoinfected patient. Subgenomic analysis of the HCV core gene suggested that 5 patients developed delayed recurrence of HCV infection. Overall, the cumulative recurrence rate of HCV infection was 2.3% (0.4%/year; 95% confidence interval [CI]=0.9%∼5.5%). The cumulative HBsAg seroclearance rate was 30.0% (95% CI=21.5%∼42.0%); with 33.1% (95% CI=21.8%∼50.1%) in 48-week combination therapy group and 24.3% (95% CI=13.7%∼42.9%) in 24-week therapy group. Conclusion: Peginterferon alfa-2a and ribavirin therapy provides a good durability of HCV SVR and a high accumulative HBsAg seroclearance rate in patients dually infected with HCV and HBV. (HEPATOLOGY 2013.).Hepatology 01/2013; · 11.66 Impact Factor -
Article: Virological predictors of response to retreatment in hepatitis C genotype 2 infected patients.
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ABSTRACT: BACKGROUNDAIMS: The impact of virological factors and interleukin-28B (IL-28B) genetic variants on retreatment of hepatitis C virus genotype 2 (HCV-2) treatment-experienced patients remains unknown. On-treatment virological responses and IL-28B rs8099917 genotype were determined in 46 HCV-2 treatment-experienced patients (42 previous relapsers; four previous non-responders) retreated with 24-week peginterferon/ribavirin. Forty (87.0%) patients carried the rs8099917 TT genotype and 6 patients (13.0%) carried the TG/GG genotype. The sustained virological response (SVR; seronegativity of HCV RNA throughout 24 weeks of the post-treatment follow-up period) rate was 71.7%. Compared with previous non-responders, previous relapsers had a significantly higher SVR rate (78.6% vs. 0%, P = 0.004) and a lower relapse rate (17.5% vs. 100%, P = 0.04). All the previous non-responders were with the rs8099917 TT genotype. As for those who relapsed, treatment responses, including the rates of rapid virological response (RVR, 80.6% vs. 66.7%, P = 0.59), early virological response (EVR, 97.2% vs. 83.3%, P = 0.27), end-of-treatment virological response (97.2% vs. 83.3%, P = 0.27) and SVR (80.6% vs. 66.7%, P = 0.59) and relapse rate (17.1% vs. 20.0%, P = 1) did not differ significantly between patients with the rs8099917 TT and those with the non-TT genotype. Multivariate analysis revealed that the most important factor predictive of an SVR in the retreatment of HCV-2 was previous relapse; the only factor predictive of an SVR for previous relapsers was the achievement of an EVR. Compared with the achievement of a RVR, the attainment of an EVR was more accurate in predicting an SVR (88% vs. 74%). Peginterferon/ribavirin is effective in the retreatment of HCV-2 relapsers, especially among those who achieved an EVR.PLoS ONE 01/2013; 8(3):e58882. · 4.09 Impact Factor
