SPP1 polymorphisms associated with HBV clearance and HCC occurrence.

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.