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Genomics Inform > Volume 6(4); 2008 > Article
DOI: https://doi.org/10.5808/gi.2008.6.4.181   
Polymorphisms in RAS Guanyl-releasing Protein 3 are Associated with Chronic Liver Disease and Hepatocellular Carcinoma in a Korean Population.
Ah Reum Oh, Seung Ku Lee, Min Ho Kim, Jae Youn Cheong, Sung Won Cho, Kap Seok Yang, KyuBum Kwack
1Medical Genomics Laboratory, Graduate School of Life Science and Biotechnology, Pochon CHA University, Seongnam 463-836, Korea.
2Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon 442-721, Korea.
3Macrogen Inc. 60-24, Seoul 153-781, Korea. kbkwack@cha.ac.kr, kbkwack@gmail.com
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.
Keywords: chronic liver disease (CLD); hepatocellular carcinoma (HCC); hepatitis B virus (HBV); phospholipase C gamma 1; single nucleotide polymorphism (SNP)


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