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rs2230201 polymorphism may dictate complement C3 levels and response to treatment in chronic hepatitis C patients
S J Chowdhury1, V K Karra, P K Gumma
1Department of Medicine, Maulana Azad Medical College, Delhi University, New Delhi, India; Department of Biotechnology, Gauhati University, Guwahati, India.
Insights
Serum C3 levels and rs2230201 genotypes impact chronic hepatitis C treatment response. Lower C3 levels and specific genotypes predict poor outcomes, suggesting potential therapeutic targets for sustained virologic response.
Area of Science:
- Immunology
- Genetics
- Hepatology
Background:
- The predictors of treatment response in chronic hepatitis C (CHC) patients remain incompletely understood.
- Serum C3 concentration is a key indicator of complement activity, and C3 deficiency is linked to recurrent infections.
Purpose of the Study:
- To investigate the association between serum C3 levels, C3 functional single nucleotide polymorphisms (SNPs), and treatment response in CHC patients.
- To determine if C3 genetic variations influence C3 serum levels and impact the achievement of sustained virologic response (SVR).
Main Methods:
- Serum C3 levels were measured using ELISA in 132 CHC patients and 81 healthy controls.
- Three functional C3 SNPs, including rs2230201, were genotyped using SSP PCR.
- Treatment response was assessed in patients receiving Pegylated Interferon + Ribavirin.
Main Results:
- Healthy individuals exhibited significantly higher serum C3 levels (88.5 ± 19 mg/dL) compared to CHC patients (56 ± 18 mg/dL).
- The rs2230201 CC genotype was prevalent in responders (33/36), while non-responders predominantly carried non-CC genotypes (9/12).
- A serum C3 level below 53 mg/dL predicted SVR with 63.89% sensitivity and 66.67% specificity.
Conclusions:
- The 'C' allele of rs2230201 is associated with elevated serum C3 levels, potentially conferring an advantage for achieving SVR in the homozygous state.
- Patients with serum C3 levels <53 mg/dL and non-CC genotypes at rs2230201 may have a reduced likelihood of responding to CHC treatment.
- These findings suggest that C3 levels and rs2230201 genotype could serve as biomarkers for predicting treatment outcomes in CHC.
Abstract:
The basis of response of chronic hepatitis C (CHC) patients to treatment is still unclear, and there may be many other factors which influence treatment outcome other than the existing ones. The serum concentration of C3 closely reflects the total complement activity, and individuals affected by C3 deficiency suffer from recurrent pyogenic infections. This study aims to find out relationship between levels of C3 in serum and its functional SNPs with response to treatment. The study included 132 CHC patients of which 48 received Pegylated IFN+Ribavirin and 81 controls. C3 levels and its three known functional SNP's genotyped by ELISA and SSP PCR, respectively. C3 Level of the healthy group was significantly higher (88.5 ± 19 mg/dL) when compared to CHC group (56 ± 18 mg/dL; P < 0.001). Thirty-three of 36 responders were rs2230201 CC genotype carriers, whereas 9 of 12 nonresponders were non-CC genotype. The 'C' allele of rs2230201 was found to be associated with increased serum C3 levels when compared to other genotypes in healthy group, whereas CT genotype was associated with lowered serum C3 in CHC group. A serum C3 value of <53 mg/dL was predictive of SVR with sensitivity 63.89% and specificity 66.67%. The study supports the observation that rs2230201 'C' allele is associated with increase of serum C3 levels when compared to 'T' allele which may confer advantage in attaining SVR when present in homozygous condition. The study suggests that patients with serum C3 value <53 mg/dL and non-CC genotypes may not respond to treatment.
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