SPP1 polymorphisms associated with HBV clearance and HCC occurrence

Abstract

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 = 1,069) 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, P(corr) = 0.02). By Cox relative hazard analysis, both SPP1-ht2 and -1,800G > 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, P(corr) = 0.01 and RH = 1.85, P = 0.003, P(corr) = 0.01, respectively). CONCLUSION: Our findings suggest that SPP1 polymorphisms might be among the genetic factors for HBV clearance and/or HCC occurrence.