A Polymorphism in the Microsomal Triglyceride Transfer Protein Can Predict the Response to Antiviral Therapy in Egyptian Patients with Chronic Hepatitis C Virus Genotype 4 Infection

Abstract

Background/AimsA polymorphism in the microsomal triglyceride transfer protein (MTP) is associated with hepatic fibrosis, and carriers showed higher levels of steatosis, higher levels of hepatitis C virus (HCV) RNA and advanced fibrosis. The aim of this study was to study MTP expression pattern in HCV patients and impact of the MTP polymorphism on the response to antiviral therapy.MethodsOne hundred consecutive naive HCV genotype 4 patients were recruited to receive antiviral therapy, and 40 control subjects were also recruited. Demographic, laboratory, and histopathology data were collected. DNA was isolated, and the samples were subjected to polymerase chain reaction analysis and genotyping for MTP by restriction fragment length polymorphism analysis.ResultsPatients and controls were age- and sex-matched (male/female, 56/44, age, 39.2±7.8 years for patients with HCV; male/female, 18/22, age, 38.1±8.1 years for controls). MTP single nucleotide polymorphisms (SNPs) (GG, GT, TT) and alleles (G, T) in the patients versus the controls were 70%, 21%, 9% & 80.5%, 19.5% versus 10%, 87.5%, 2.5% & 53.8%, 46.3%, respectively (p=0.0001). The sustained viral response (SVR) of the patients was 60%. SNPs in MTP genotypes (GG, GT, and TT) and alleles (G and T) in the responders and nonresponders were 71.7%, 25%, 3.3% & 84.2%, 15.8% versus 67.5%, 15%, 17.5% & 75%, 25% (p=0.038 and p=0.109, respectively). A multivariate analysis showed that the GT genotype was an independent predictor of SVR (area under the curve 90% and p=0.0001).ConclusionsMTP could be a new predictor for SVR to antiviral therapy in patients with HCV genotype 4 infection.

Meta-analysis

“…Sub-group-analysis by prospective and retrospective studies showed similar SVR rates: 53% (CI: 50–56%) in forty-three prospective studies[10, 11, 13–16, 18, 27, 28, 34, 38–42, 46, 48, 53–56, 62, 63, 65–67, 69, 72, 73, 75–78, 80, 81, 83, 84, 88, 90, 91, 93, 95, 96] and 53% (CI: 46–59%) in eight retrospective studies[12, 35, 37, 45, 59, 71, 79, 85]. Significant heterogeneity was observed in both sub-group analyses with I 2 >50% (Figure 4).…”

Genetic variation in the microsomal triglyceride transfer protein (−493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus

“…Additionally, the GG and GT genotypes were considered independent protective factors against steatosis in patients with chronic hepatitis C and HCV genotype 1 and non-1 [32]. Finally, Saad et al [9] also studied this polymorphism, although not in relation to steatosis, and they reported an association between the GT and TT genotypes and severe fibrosis and cirrhosis ( P  = 0.0001).…”

“…The function of MTTP is related to the assembly and secretion of low-density lipoproteins (LDLs), such as very low-density lipoproteins (VLDLs) [5, 8, 9]. A functional SNP in the promoter region of MTTP (−493G/T) has been found to play an important role in the regulation of gene expression and influences the concentration of circulating LDL in the plasma of healthy individuals [10].…”