MTTP polymorphisms and hepatic steatosis in individuals chronically infected with hepatitis C virus

Prata, Thamiris Vaz Gago; Silva, Dayane de Souza Rodrigues da; Manchiero, Caroline; Dantas, Bianca Peixoto; Mazza, Celso Carmo; Nunes, Arielle Karen da Silva; Abdala, Edson; Figueiredo, Gerusa Maria; Tengan, Fátima Mitiko; Magri, Mariana Cavalheiro

doi:10.1007/s00705-019-04352-4

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…This study began with a comprehensive screening based on strict inclusion and exclusion criteria, and subsequently included novel publications from recent years. The result found the dominant model (GT + TT) is positively correlated with an increased risk of liver steatosis associated with hepatitis C. Notably, the risk of liver steatosis increased significantly when the HCV genotype 3 was combined with a dominant model of MTTP mutations, which is consistent with the findings by Tao Cai [ 25 , 26 ]. In contrast, no correlation to hepatic steatosis susceptibility was observed in other mutation models.…”

Section: Discussionsupporting

confidence: 88%

“…In the HCV genotype 3, the core protein has the strongest effect on lipid accumulation by inhibiting the expression of the MTTP protein and preventing the secretion of lipoproteins [ 7 , 34 ]. Accordingly, patients with the HCV genotype 3 have an increased risk of liver steatosis when carrying the dominant MTTP genotype [ 26 ]. Since the expression levels of the MTTP gene dynamically changes during the early and late stages of HCV infection, assessing the risk of liver steatosis depends on monitoring changes in MTTP genotype expression during early HCV infection.…”

Section: Discussionmentioning

confidence: 99%

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

Wang,

Cao,

Guo

et al. 2023

Lipids Health Dis

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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.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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

Wang,

Cao,

Guo

et al. 2023

Lipids Health Dis

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“…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) 213 . Hepatic SREBP is also upregulated in chronic HCV infection, 208 corresponding to increases in de novo lipogenesis that are essential for HCV replication and release, according to Narayanan et al 214 …”

Section: Clds Associated With Hepatic Steatosis (Slds)mentioning

confidence: 99%

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

Koenig,

Tan,

Abdelaal

et al. 2024

Aliment Pharmacol Ther

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SummaryBackgroundHepatic steatosis is a common finding in liver histopathology and the hallmark of metabolic dysfunction‐associated steatotic liver disease (MASLD), formerly known as non‐alcoholic fatty liver disease (NAFLD), whose global prevalence is rising.AimsTo review the histopathology of hepatic steatosis and its mechanisms of development and to identify common and rare disease associations.MethodsWe reviewed literature on the basic science of lipid droplet (LD) biology and clinical research on acute and chronic liver diseases associated with hepatic steatosis using the PubMed database.ResultsA variety of genetic and environmental factors contribute to the development of chronic hepatic steatosis or steatotic liver disease, which typically appears macrovesicular. Microvesicular steatosis is associated with acute mitochondrial dysfunction and liver failure. Fat metabolic processes in hepatocytes whose dysregulation leads to the development of steatosis include secretion of lipoprotein particles, uptake of remnant lipoprotein particles or free fatty acids from blood, de novo lipogenesis, oxidation of fatty acids, lipolysis and lipophagy. Hepatic insulin resistance is a key feature of MASLD. Seipin is a polyfunctional protein that facilitates LD biogenesis. Assembly of hepatitis C virus takes place on LD surfaces. LDs make important, functional contact with the endoplasmic reticulum and other organelles.ConclusionsDiverse liver pathologies are associated with hepatic steatosis, with MASLD being the most important contributor. The biogenesis and dynamics of LDs in hepatocytes are complex and warrant further investigation. Organellar interfaces permit co‐regulation of lipid metabolism to match generation of potentially toxic lipid species with their LD depot storage.

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“…Empregou-se a equação recomendada para esse tipo de estudo: n=π (1-π) /e2, onde n = tamanho da amostra (mínimo requerido), π = proporção de interesse, e = erro padrão (Kirkwood;Sterne, 2006). Nota: os SNPs -164T/C, -400A/T, H297Q e -493G⁄T foram previamente genotipados nesse grupo (Magri et al, 2017;Prata et al, 2019a, Prata, 2019b. No presente estudo esses dados foram submetidos a novas análises estatísticas e genéticas.…”

Section: Tamanho De Amostra Grupo 1 -Portadores Crônicos Do Hcvunclassified

“…Além disso, foi observado uma associação estatisticamente significante entre os alelos mutados para os polimorfismos -164T/C e -400A/T juntamente com a infecção pelo genótipo 3 do HCV e a ocorrência de esteatose nesses pacientes. Desse modo, sugere-se que a combinação de fatores hospedeiros e fatores virais podem potencialmente ser utilizados para prever a esteatose hepática(Prata et al, 2019a). Na Tabela 3 estão apresentados alguns estudos que avaliaram a influência de polimorfismos no gene MTTP em pacientes com hepatite C. não está clara a relação entre os SNPs no gene MTTP e a susceptibilidade para resistência à insulina e esteatose hepática em portadores crônicos do HCV.…”

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Influência de polimorfismos no gene MTTP nos níveis de lipídeos e na esteatose associada à infecção crônica pelo vírus da hepatite C

Prata

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Aos meus pais, João e Elisabete, pelo apoio incondicional e por sempre me incentivarem a continuar buscando novos desafios.À minha irmã, Cynthia, por todo o carinho, apoio e força nos momentos mais difíceis.Ao meu marido Pedro, que compartilha essa caminhada comigo, incentivando e vibrando a cada conquista. À minha orientadora Profa. Dra. Mariana Cavalheiro Magri, por tantos ensinamentos durante esses anos. Sou muito grata por todas as oportunidades, confiança, paciência, disponibilidade e ajuda em diversos momentos. Foi uma honra ter sido sua aluna! À minha co-orientadora Profa. Dra. Fátima Mitiko Tengan, por todo o auxílio, ensinamentos e oportunidades de crescimento concedidas durante esses anos. Aos Professores Dr. Edson Abdala, Dra. Alice Tung Wan Song e Dra. Nayara Izabel Viana pelas diversas contribuições e recomendações durante o exame de qualificação.Ao Prof. Dr. Antonio Alci Barone, um grande exemplo para todos.A toda a equipe do LIM-47, pela amizade, apoio e ajuda com esse trabalho. Além disso, sou muito grata por tantos momentos alegres e pelo convívio nesses anos.

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MTTP polymorphisms and hepatic steatosis in individuals chronically infected with hepatitis C virus

Cited by 8 publications

References 21 publications

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

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

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

Influência de polimorfismos no gene MTTP nos níveis de lipídeos e na esteatose associada à infecção crônica pelo vírus da hepatite C

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