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Difference of polymorphism VEGF-gene rs699947 in Indonesian chronic liver disease population
Neneng Ratnasari1, Siti Nurdjanah1, Ahmad Hamim Sadewa2
1Department of Internal Medicine, Faculty of Medicine Gadjah Mada University/ Dr. Sardjito Hospital, Yogyakarta, Indonesia.
Insights
The VEGF gene polymorphism rs699947, specifically allele A and SNP A>C, may predict the progression of liver disease from healthy states to chronic hepatitis, liver cirrhosis, or hepatocellular carcinoma, and from liver cirrhosis to hepatocellular carcinoma.
Area of Science:
- Genetics and Molecular Biology
- Hepatology
- Oncology
Background:
- Vascular Endothelial Growth Factor (VEGF) gene polymorphism rs699947 is linked to hepatocellular carcinoma (HCC) outcomes.
- Limited research exists on VEGF gene polymorphisms and chronic liver disease progression.
- This study investigates VEGF rs699947 variations in Indonesian patients with chronic hepatitis (CH), liver cirrhosis (LC), and HCC.
Purpose of the Study:
- To analyze differences in VEGF gene polymorphism rs699947 among Indonesian individuals with chronic liver conditions.
- To determine the association of VEGF rs699947 with disease progression in chronic liver disease.
Main Methods:
- A cross-sectional study involving 123 chronic liver disease patients (CH, LC, HCC) and 59 healthy controls.
- DNA sequencing of the VEGF gene rs699947 using specific primers and Applied Bio systems.
- Statistical analysis using STATA version 11.0, with significance set at P<0.05.
Main Results:
- Significant differences in allele A and C distributions of VEGF rs699947 were observed between healthy individuals and LC/HCC patients, and between CH and LC patients.
- Allele A and SNP A>C showed potential as predictors for disease progression from healthy to CH, LC, or HCC, and from LC to HCC.
- Hepatitis B (HBV) was the predominant etiology across all chronic liver disease groups.
Conclusions:
- The occurrence of allele A and SNP A>C in the VEGF gene (-2578) may serve as a predictive marker for liver disease progression.
- These findings contribute to understanding the genetic factors influencing the development and advancement of chronic liver diseases.
Background:
The VEGF gene polymorphism rs699947 related to clinical pathology, mortality, and recurrence of HCC. Few studies mentioned an association between VEGF gene polymorphisms with illness progression in chronic liver disease. We aimed to explore differences of VEGF gene polymorphism rs699947 in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma patients in Indonesian population.
Methods:
A cross-sectional study with consecutive sampling and without matching was performed during a 3 years period (2011-2014) at Dr. Sardjito General Hospital Yogyakarta, Indonesia. Blood DNA was sequenced from 123 subjects with chronic liver diseases [39 chronic hepatitis (CH), 39 liver cirrhosis (LC), and 45 hepatocellular carcinoma (HCC)]. 59 healthy subjects also participated. Using isolated VEGF genes for specific primers for rs699947, blood samples were examined by targeting DNA sequences with Applied Bio systems. All data were analyzed using STATA version 11.0 with significance level at P<0.05.
Results:
The mean of age in HCC and LC subjects were older than in CH and healthy (P value <0.05); there were more males in LC, HCC and the healthy groups but not in CH (P>0.05). HBV was the dominant etiology in HCC, LC, and CH besides HCV and non HBV-HCV (P<0.05). There were significant differences in the SNP -2578 distributions of allele C compared to allele A in all subjects (healthy vs. LC, and HCC; LC vs. CH (P<0.05), but no significant difference A>C vs. C>C, and genotypes distribution. Proportion of SNP -2578 A>C vs. C>C CH 1.8:1; HCC 1.4:1; healthy 1.7:1; but its proportion in LC was inversed (1:1.2). Genotype A was low in all subjects (5%-11%). Significant difference of allele distribution was found in healthy vs. LC, and HCC; CH vs. LC. Based on HWE analyses, distribution of allele C was dominant. There were not significant differences in deletion, insertion-deletion at -2547 until -2526, and haplotype (Ht) CCGACCCC (P>0.05). The OR analyses of allele and SNP showed that allele A can be a predictor of disease progression in LC to HCC (OR 2.26) and healthy to LC (OR 1.65); and SNP A>C also can be a predictor in healthy to HCC (OR 1.41) and CH (OR 1.14).
Conclusion:
The occurrence of allele A and SNP A>C VEGF gene (-2578) might predict illness progression from healthy to CH, LC or HCC and LC to HCC.
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