Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis

Author(s)

Thamiris Vaz Gago Prata ^[1] ; Caroline Manchiero ^[2] ; Bianca Peixoto Dantas ^[3] ; Arielle Karen da Silva Nunes ^[4] ; Fátima Mitiko Tengan ; Mariana Cavalheiro Magri ^[6]

Affiliation

^[1] Universidade de São Paulo (HCFMUSP). Faculdade de Medicina. Hospital das Clínicas - Brasil

^[2] Universidade de São Paulo (HCFMUSP). Faculdade de Medicina. Hospital das Clínicas - Brasil

^[3] Universidade de São Paulo (HCFMUSP). Faculdade de Medicina. Hospital das Clínicas - Brasil

^[4] Universidade de São Paulo (HCFMUSP). Faculdade de Medicina. Hospital das Clínicas - Brasil

^[6] Universidade de São Paulo (HCFMUSP). Faculdade de Medicina. Hospital das Clínicas - Brasil

• Document type: Journal article
• Source: Clinics; v. 77, 2022-10-10.

Abstract

Abstract Background: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. Objective: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. Methods: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. Results: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. Conclusion: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis. (AU)

• FAPESP's process: 16/19690-5 - Genetic changes in MTTP gene and its relation to plasma lipid levels and hepatic steatosis in patients with chronic hepatitis C
• Grantee: Mariana Cavalheiro Magri
• Support Opportunities: Regular Research Grants