IJE Advance Access published online on May 11, 2007
International Journal of Epidemiology, doi:10.1093/ije/dym093
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SPP1 polymorphisms associated with HBV clearance and HCC occurrence
1 Department of Genetic Epidemiology, SNP Genetics, Inc., Rm 1407, 14th floor, Complex B, WooLim Lion's Valley, 371-28, Gasan-Dong, Geumcheon-Gu, Seoul, 153-803, Republic of Korea.
2 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-dong, Chongro-Gu, Seoul, 110-744, Republic of Korea.
* Corresponding author. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-Dong, Chongno-Gu, Seoul, 110-744, Republic of Korea. E-mail: hsleemd{at}snu.ac.kr
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Abstract |
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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.
Keywords SPP1, HBV, HCC, single-nucleotide polymorphism, haplotype
Hyoung Doo Shin and Byung Lae Park contributed equally to this work.
Accepted 3 April 2007