Résumé :
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[BDSP. Notice produite par INIST-CNRS sM69R0xa. Diffusion soumise à autorisation]. Background : Secreted phosphoprotein-1 (SPP1) is a secreted arginine-glycine-aspartate (RGD) - containing phosphoprotein. SPP1 is overexpressed in metastatic hepatocellular carcinoma (HCC), and therefore could act as both a diagnostic marker and a potential therapeutic target for metastatic HCC. We investigated the genetic polymorphisms in SPP1 to determine whether it is a potential candidate gene for a host genetic study of hepatitis B virus (HBV) clearance and HCC occurrence. Methods : Five genetic variants in SPP1 were genotyped by TaqMan assay and the genetic association with HBV clearance and HCC occurrence was analysed. Results : Genetic association analysis of SPP1 polymorphisms with an HBV cohort (n=1069) from the Korean population revealed that the most common haplotype (SPP1-ht2 [T-T-C-T-A]) was associated with HBV clearance. The frequency of the SPP1-ht2-bearing genotype in the chronic carrier (CC) group was higher than in the spontaneously recovered (SR) group (OR=1.44 [95% CI 1.11-1.87], P=0.006, Pcorr=0.02). By Cox relative hazard analysis, both SPP1-ht2 and - 1800G>T were associated with age of HCC occurrence among chronic hepatitis patients, e.g. ht2/h2-and 1800T/T-bearing patients showed earlier progression to HCC than did others (RH=1.85, P=0.004, Pcorr=0.01 and RH=1.85, P=0.003, Pcorr=0.01, respectively). Conclusion : Our findings suggest that SPP1 polymorphisms might be among the genetic factors for HBV clearance and/or HCC occurrence.
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