TGFBR3 Polymorphisms and Its Haplotypes Associated with Chronic Hepatitis B Virus Infection and Age of Hepatocellular Carcinoma OccurrenceKim J.-H. · Yu S.J. · Park B.-L. · Cheong H.S. · Pasaje C.F.A. · Bae J.S. · Lee H.-S. · Shin H.D. · Kim Y.J.
aDepartment of Life Science, Sogang University, bDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, and cDepartment of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea
Objective: Hepatocellular carcinoma (HCC) is one of the most common cancers and is mainly caused by viral infections including hepatitis B virus (HBV). Recently, the decreased expression level of the transforming growth factor, beta receptor III (TGFBR3) gene, has been implicated in HCC and other human cancers. This study investigated whether TGFBR3 polymorphisms might be associated with HBV clearance and HCC occurrence. Methods: This study identified 27 single nucleotide polymorphisms (SNPs) in the exon, promoter, and exon-intron boundary regions of TGFBR3 by resequencing in 24 individuals. Then, 9 SNPs in the promoter and exons of the gene were genotyped from 1,065 Koreans composed of 637 chronic carriers (CC) and 428 spontaneously recovered (SR) subjects. Results: Two SNPs, rs1805113 (Phe676Phe) in exon 13 and rs1805117 in 3′-UTR (p = 0.009 and p = 0.008, respectively) were significantly associated with HBV clearance. In addition, Cox relative hazards analyses revealed that haplotype BL2_ht2 showed a significant association with the age of HCC occurrence among chronic HBV patients (relative hazard = 1.38; p = 0.007). Conclusion: Our findings suggest that TGFBR3 polymorphisms and its haplotypes might be associated with HBV clearance and age of HCC occurrence.
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