Laboratorio de Investigacao Médica em Hepatologia por Virus (LIM-47), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.
Laboratorio de Investigacao Médica em Hepatologia por Virus (LIM-47), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil; Departamento de Molestias Infecciosas e Parasitarias, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil.
Clinics (Sao Paulo). 2022 Aug 22;77:100094. doi: 10.1016/j.clinsp.2022.100094. eCollection 2022.
Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis.
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.
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.
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.
The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.
慢性丙型肝炎的特征是肝功能进行性恶化，并涉及代谢并发症，如肝脂肪变性。
本研究旨在探讨宿主和病毒特征与微粒体甘油三酯转移蛋白（MTTP）基因中的 -493G/T（rs1800591）、I128T（rs3816873）、Q95H（rs61733139）和 Q244E（rs17599091）单核苷酸多态性（SNP）与慢性丙型肝炎肝脂肪变性的关系。
采用 PCR-RFLP 法对 SNP 进行基因分型，并结合宿主和病毒特征，采用多种遗传模型进行多元逻辑回归分析。
作者分析了 236 例慢性丙型肝炎患者，其中 53%存在肝脂肪变性。突变等位基因频率>5%，基因型处于 Hardy-Weinberg 平衡（p≥0.05）。结果发现，丙型肝炎病毒基因型 3 感染（OR=2.74，95%CI 1.24-6.06，p=0.013）、女性（OR=2.28，95%CI 1.21-4.28，p=0.011）和中重度肝炎症活动（A2-A3）（OR=3.61，95%CI 1.86-7.01，p<0.001）的患者发生脂肪变性的风险更高。多因素逻辑回归分析结果显示，对于-493G/T SNP，当 GT/TT 基因型（显性模型）和 GT 基因型（共显性模型）分别与丙型肝炎病毒基因型 3 感染相结合时，脂肪变性的风险分别增加了 11.51 倍（95%CI 2.08-63.59，p=0.005）和 15.69 倍（95%CI 2.46-99.85，p=0.004）。对于 I128T SNP，当 IT/TT 基因型（显性模型）和 IT 基因型（共显性模型）分别与丙型肝炎病毒基因型 3 感染相结合时，脂肪变性的风险分别增加了 8.51 倍（95%CI 1.59-45.54，p=0.012）和 8.40 倍（95%CI 1.51-46.91，p=0.015）。
本研究表明，病毒基因型与 MTTP 基因中的 -493G/T 和 I128T SNPs 联合影响肝脂肪变性。
