Rs2230201 polymorphism may dictate complement C3 levels and response to treatment in chronic hepatitis C patients

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.