Association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C: a systematic review and meta-analysis

Abstract

Background Hepatitis C has been associated with the development of hepatic steatosis, which increases the risk of liver cancer. The microsomal triglyceride transporter protein (MTTP), is a lipid transport protein that mediates lipid metabolism and CD1d antigen presentation. The study aimed to explore the association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C. Methods The database “Pubmed, Cochrane library, CNKI, Web of science, Embase and CBM” were retrieved to identify the literature. The quality of the selected literature was evaluated using the “the Newcastle–Ottawa Scale” (NOS). Relevant data was extracted and analyzed using the Stata software. Heterogeneity was expressed by “Cochran's Q and I2”, with I2 ≥ 50% or P < 0.05 indicating high heterogeneity. A random-effects model and subgroup analysis were conducted to identify the sources of heterogeneity. We also used “Funnel plots”, “Egger’s tests” and “Begg’s tests” to evaluate biases in the literature. Results The study found a significant and positive association between liver steatosis and the HCV genotype 3 with a dominant model of the MTTP genotype (-493G/T) (OR = 11.57, 95%CI: 4.467–29.962, P < 0.001). In contrast, no correlation was found between hepatic steatosis and either the recessive, homozygous or heterozygous models (OR = 1.142, P = 0.5; OR = 1.581, P = 0.081; OR = 1.029, P = 0.86). There was no significant publication biases, as measured by the Funnel plot, and the Egger’s and Begg's tests. Finally, sensitivity analysis showed the obtained results are stable. Conclusions Dominant mutations in the T allele of the MTTP genotype (-493G/T) increase susceptibility to hepatic steatosis in patients presenting with the HCV genotype 3.

Review article: Hepatic steatosis and its associations with acute and chronic liver diseases

“…210 Moreover, the single nucleotide polymorphism (SNP) MTTP −493G/T (rs1800591) may be associated with more severe steatosis in CHC, 210 and heterozygosity for the minor allele (T) has synergistic effects on susceptibility to hepatic steatosis in HCV genotype 3 infection. 211 The minor allele increases transcription of MTTP, which encodes MTP. 211 To resolve this apparent discrepancy with the known inhibitory effect of HCV core protein on MTP, 212 Mirandola et al 210 propose that upregulation of MTTP benefits viral replication early in infection, while chronic inhibition of MTP contributes to viral persistence.…”

“…211 The minor allele increases transcription of MTTP, which encodes MTP. 211 To resolve this apparent discrepancy with the known inhibitory effect of HCV core protein on MTP, 212 Mirandola et al 210 propose that upregulation of MTTP benefits viral replication early in infection, while chronic inhibition of MTP contributes to viral persistence. Other MTTP variants that have been reported to contribute to hepatic steatosis in genotype 3 infection include −164T/C (rs1800804) and −400A/T (rs1800803).…”