Polymorphisms in RAS Guanyl-releasing Protein 3 are Associated with Chronic Liver Disease and Hepatocellular Carcinoma in a Korean Population.
- Author:
Ah Reum OH
1
;
Seung Ku LEE
;
Min Ho KIM
;
Jae Youn CHEONG
;
Sung Won CHO
;
Kap Seok YANG
;
KyuBum KWACK
Author Information
1. Medical Genomics Laboratory, Graduate School of Life Science and Biotechnology, Pochon CHA University, Seongnam 463-836, Korea.
- Publication Type:Original Article
- Keywords:
chronic liver disease (CLD);
hepatocellular carcinoma (HCC);
hepatitis B virus (HBV);
phospholipase C gamma 1;
single nucleotide polymorphism (SNP)
- MeSH:
Alleles;
Carcinoma, Hepatocellular;
GTP Phosphohydrolases;
Guanosine Triphosphate;
Haplotypes;
Hepatitis B virus;
Humans;
Intercellular Signaling Peptides and Proteins;
Liver;
Liver Diseases;
Phospholipase C gamma;
Phosphotransferases;
Polymorphism, Single Nucleotide;
Polyphosphates;
Signal Transduction
- From:Genomics & Informatics
2008;6(4):181-191
- CountryRepublic of Korea
- Language:English
-
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=1.81~2.61, p=0.01~0.03, 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 ~2.78, p=0.01~0.03). 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=0.42~0.66, p=0.006~0.015). Thus, our data suggest that RasGRP3 SNPs are significantly associated with an increased risk of developing HCC.
