KMID : 1132720080060040181
|
|
Genomics & Informatics 2008 Volume.6 No. 4 p.181 ~ p.191
|
|
Polymorphisms in RAS Guanyl-releasing Protein 3 are Associated with Chronic Liver Disease and Hepatocellular Carcinoma in a Korean Population
|
|
Oh Ah-Reum
Cho Sung-Won Cheong Jae-Youn Lee Seung-Ku Kim Min-Ho Yang Kap-Seok Kwack Kyu-Bum
|
|
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.
|
|
KEYWORD
|
|
chronic liver disease (CLD), hepatocellular
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|