Polymorphisms in RAS Guanyl-releasing Protein 3 are Associated with Chronic Liver Disease and Hepatocellular Carcinoma in a Korean Population
Genomics & Informatics
;
: 181-191, 2008.
Article
in English
| WPRIM
| ID: wpr-203275
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphotransferases
/
Polyphosphates
/
Haplotypes
/
Signal Transduction
/
Hepatitis B virus
/
Carcinoma, Hepatocellular
/
Polymorphism, Single Nucleotide
/
Intercellular Signaling Peptides and Proteins
/
Alleles
/
Phospholipase C gamma
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Genomics & Informatics
Year:
2008
Type:
Article
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