Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Polymorphisms in RAS Guanyl-releasing Protein 3 are Associated with Chronic Liver Disease and Hepatocellular Carcinoma in a Korean Population

  • Oh, Ah-Reum (Medical Genomics Laboratory, Graduate School of Life Science and Biotechnology, Pochon CHA University) ;
  • Lee, Seung-Ku (Medical Genomics Laboratory, Graduate School of Life Science and Biotechnology, Pochon CHA University) ;
  • Kim, Min-Ho (Medical Genomics Laboratory, Graduate School of Life Science and Biotechnology, Pochon CHA University) ;
  • Cheong, Jae-Youn (Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine) ;
  • Cho, Sung-Won (Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine) ;
  • Yang, Kap-Seok (Macrogen Inc.) ;
  • Kwack, Kyu-Bum (Medical Genomics Laboratory, Graduate School of Life Science and Biotechnology, Pochon CHA University)
  • Published : 2008.12.31
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Abstract

RAS guanyl-releasing protein 3 (RasGRP3), a member of the Ras subfamily of GTPases, functions as a guanosine triphosphate (GTP)/guanosine diphosphate (GDP)-regulated switch that cycles between inactive GDP- and active GTP-bound states during signal transduction. Various growth factors enhance hepatocellular carcinoma (HCC) proliferation via activation of the Ras/Raf-1/extracellular signal-regulated kinase (ERK) pathway, which depends on RasGRP3 activation. We investigated the relationship between polymorphisms in RasGRP3 and progression of hepatitis B virus (HBV)-infected HCC in a Korean population. Nineteen RasGRP3 SNPs were genotyped in 206 patients with chronic liver disease (CLD) and 86 patients with HCC. Our results revealed that the T allele of the rs7597095 SNP and the C allele of the rs7592762 SNP increased susceptibility to HCC (OR=1.55, p=0.04 and OR=1.81${\sim}$2.61, p=0.01${\sim}$0.03, respectively). Moreover, patients who possessed the haplotype (ht) 1 (A-T-C-G) or diplotype (dt) 1 (ht1/ht1) variations had increased susceptibility to HCC (OR=1.79${\sim}$2.78, p=0.01${\sim}$0.03). In addition, we identified an association between haplotype1 (ht1) and the age of HCC onset; the age of HCC onset are earlier in ht1 +/+ than ht1 +/- or ht1 -/- (HR=0.42${\sim}$0.66, p=0.006${\sim}$0.015). Thus, our data suggest that RasGRP3 SNPs are significantly associated with an increased risk of developing HCC.

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References

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