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Publications (2)5.7 Total impact

  • Article: Association of single-nucleotide polymorphisms in HLA class II/III region with knee osteoarthritis.
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    ABSTRACT: A genome-wide association study and a replication using Japanese, Spanish and Greek Caucasian populations have recently indicated two single-nucleotide polymorphisms (SNPs) (rs7775228 and rs10947262) associated with knee Osteoarthritis (OA) susceptibility. We have further evaluated the association in knee OA subjects from Han Chinese and Australian Caucasian origin. Two independent case-control association studies were performed using Han Chinese and Australian Caucasian populations. The two SNPs were genotyped in patients who had primary symptomatic knee OA with radiographic confirmation and/or received total knee replacement surgery as well as in matched controls. They were subjected to statistic analyses. A total of 991 OA patients and 1536 controls were genotyped. No significant difference was detected in genotype or allele frequencies of the two SNPs between knee OA and control groups in the two populations (all P>0.05). The association was also negative even after stratification by sex, body mass index (BMI) and Kellgren/Lawrence scores. The significant heterogeneity was detected between Chinese and Japanese (both P<0.05). In the Caucasian samples, no significant heterogeneity was detected (both P>0.05). The result of meta-analysis showed significant association between knee OA and rs10947262 in total subjects [summary OR=1.26, 95%confidence intervals (CI)=1.07-1.27, P=3 × 10(-8)] and in Caucasian samples (summary OR=1.28, 95%CI=1.04-1.57, P=0.02). We demonstrated no association between the two SNPs in human leukocyte antigen (HLA) class II/III region and knee OA in Han Chinese population. A significant association was detected between SNP rs10947262 and knee OA in Caucasian subjects. Further replication studies are required to identify the impact of controversial association.
    Osteoarthritis and Cartilage 11/2010; 18(11):1454-7. · 3.90 Impact Factor
  • Article: Mechanism-based inhibition of CYP1A2 by antofloxacin, an 8-NH2 derivative of levofloxacin in rats.
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    ABSTRACT: A recent focus was to investigate whether antofloxacin, an 8-NH(2) derivative of levofloxacin, inhibited cytochrome P450 (CYP) 1A2 activity in rats. Phenacetin, the representative substrate of CYP1A2, was used as the model drug to evaluate the activity of CYP1A2. In an in vivo study, an oral single dose of antofloxacin (20 mg kg(-1)) did not affect the pharmacokinetic behaviour of phenacetin, but a multidose (20 mg kg(-1) twice daily for 7.5 days) significantly increased phenacetin's area under the curve (AUC). In an in vitro study, only when pre-incubated with beta-nicotinamide adenine dinucleotide phosphate, a reduced form (NADPH) system in rat liver microsomes, did antofloxacin inhibit phenacetin O-deethylation. The inhibition was NADPH-, pre-incubation time-, and antofloxacin concentration-dependent. A physiologically based pharmacokinetic model with mechanism-based inhibition was successfully developed for predicting the interaction between antofloxacin and phenacetin in vivo from the in vitro data. The simulated AUC was 1.4-fold of the control, which was near the observed value of 1.6-fold. From the results, it can be concluded that the inhibition of CYP1A2 by antofloxacin is mechanism-based.
    Xenobiotica 05/2009; 39(4):293-301. · 1.79 Impact Factor