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.

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