MTP genetic variants associated with non-alcoholic fatty liver in metabolic syndrome patients

Gouda, Weaam; Ashour, Esmat; Shaker, Yehia; Ezzat, Wafaa M.

doi:10.1016/j.gendis.2017.09.002

Cited by 15 publications

(22 citation statements)

References 49 publications

(58 reference statements)

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“…Microsomal triglyceride transfer protein (MTTP) acts as a chaperon involved in apolipoprotein B (ApoB) lipoprotein assembly [143]. The 493 G/T polymorphism has been associated with NAFLD development and metabolic syndrome [144].…”

Section: Pathophysiological Featuresmentioning

confidence: 99%

Pathophysiological, Molecular and Therapeutic Issues of Nonalcoholic Fatty Liver Disease: An Overview

Marchisello

Pino

Purrello

et al. 2019

IJMS

143

140

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Nonalcoholic Fatty Liver Disease (NAFLD) represents the leading cause of liver disease in developed countries but its diffusion is currently also emerging in Asian countries, in South America and in other developing countries. It is progressively becoming one of the main diseases responsible for hepatic insufficiency, hepatocarcinoma and the need for orthotopic liver transplantation. NAFLD is linked with metabolic syndrome in a close and bidirectional relationship. To date, NAFLD is a diagnosis of exclusion, and liver biopsy is the gold standard for diagnosis. NAFLD pathogenesis is complex and multifactorial, mainly involving genetic, metabolic and environmental factors. New concepts are constantly arising in the literature promising new diagnostic and therapeutic tools. One of the challenges will be to better characterize not only NAFLD development but overall NAFLD progression, in order to better identify NAFLD patients at higher risk of metabolic, cardiovascular and neoplastic complications. This review analyses NAFLD epidemiology and the different prevalence of the disease in distinct groups, particularly according to sex, age, body mass index, type 2 diabetes and dyslipidemia. Furthermore, the work expands on the pathophysiology of NAFLD, examining multiple-hit pathogenesis and the role of different factors in hepatic steatosis development and progression: genetics, metabolic factors and insulin resistance, diet, adipose tissue, gut microbiota, iron deposits, bile acids and circadian clock. In conclusion, the current available therapies for NAFLD will be discussed.

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Section: Pathophysiological Featuresmentioning

confidence: 99%

Pathophysiological, Molecular and Therapeutic Issues of Nonalcoholic Fatty Liver Disease: An Overview

Marchisello

Pino

Purrello

et al. 2019

IJMS

143

140

View full text Add to dashboard Cite

show abstract

“…Finally, 10 studies were retained for the present meta-analysis. [ 13 14 15 16 18 19 20 21 22 23 ] The flowchart for the literature search and selection process is illustrated in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

“…A total of 1388 cases and 1690 healthy controls were included in the present meta-analysis. Among these 10 studies, four studies were conducted in Europe,[ 15 18 20 21 ] four studies were conducted in Asia,[ 13 14 16 23 ] one study was conducted in Africa,[ 19 ] and one study was conducted in South America. [ 22 ] In addition, all patients in these four studies underwent liver biopsy,[ 13 18 20 22 ] while in the remaining six studies, patients were partially biopsied or not biopsied.…”

Section: Resultsmentioning

confidence: 99%

“…[ 22 ] In addition, all patients in these four studies underwent liver biopsy,[ 13 18 20 22 ] while in the remaining six studies, patients were partially biopsied or not biopsied. [ 14 15 16 19 21 23 ] In three studies, the control groups were hospital-based,[ 16 19 23 ] while in seven studies, the control groups were population-based. [ 13 14 15 18 20 21 22 ] For the detection of gene polymorphism, six studies used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method,[ 13 15 18 19 20 21 ] while the remaining four studies used other detection methods.…”

Section: Resultsmentioning

confidence: 99%

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The association between SNPs rs1800591 and rs3816873 of the MTTP gene and nonalcoholic fatty liver disease: A meta-analysis

Tan

Zhang

Zhao

et al. 2020

Saudi J Gastroenterol

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Background/Aims: The role of two polymorphisms rs1800591 and rs3816873 of the microsomal triglyceride transfer protein (MTTP) gene in the development of nonalcoholic fatty liver disease (NAFLD) remains controversial. A meta-analysis was conducted to determine the correlation between these MTTP polymorphisms and NAFLD. Materials and Methods: A systematic search was carried out using PubMed, Embase, and Cochrane Library to retrieve English studies that reported the relationship between MTTP polymorphisms (rs1800591 and rs3816873) and NAFLD published before February 18, 2020. Odds ratio (OR) and 95% confidence interval (CI) were used to appraise the risk of MTTP polymorphism in NAFLD. Results: A total of 10 case-control studies, including 1388 cases and 1690 healthy subjects, were included. No significant correlation between the rs1800591 (G vs. T: OR = 1.08, 95% CI = 0.68–1.70, P = 0.76) and rs3816873 (CT + CC vs. TT: OR = 1.23, 95% CI = 0.76–2.01, P = 0.398) polymorphisms of MTTP and NAFLD was found in any of the models. However, when NASH patients confirmed by liver biopsy were extracted alone for rs1800591 polymorphism analysis, it was found that the G allele significantly increased the risk of NASH under the heterozygote model (GT vs. TT: OR = 3.16, 95% CI = 1.13–8.83, P = 0.028) and dominant model (GT + GG vs. TT: OR = 3.03, 95% CI = 1.13–8.09, P = 0.027). Conclusion: The present meta-analysis revealed that the rs1800591 and rs3816873 polymorphisms of the MTTP gene are uncommon in NAFLD. However, the G allele of rs1800591 was more likely to be correlated to NASH susceptibility.

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“…ApoB100 and microsomal TG transfer protein (MTP) mediate VLDL secretion in hepatocytes. Studies have revealed that pharmacological inhibition of MTP can be used to treat hyperlipidaemia in rats with monosodium L-glutamate-induced obesity, while increases in MPT gene or protein expression can be used to treat NAFLD [33][34][35]. Studies have also indicated that upregulating PPAR-α, carnitine palmitoyltransferase-1a (CPT-1a) and fatty TG lipase (ATGL) to enhance FA oxidation and lipolysis can improve NAFLD in micee [36,37].…”

Section: Pathogenesis Of Nafld and Glycolipid Metabolismmentioning

confidence: 99%

Mutual interaction between endoplasmic reticulum and mitochondria in nonalcoholic fatty liver disease

Wang¹,

He²,

Tsai

et al. 2020

Lipids Health Dis

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Nonalcoholic fatty liver disease (NAFLD) is a common metabolic syndrome. Imbalances between liver lipid output and input are the direct causes of NAFLD, and hepatic steatosis is the pathological premise and basis for NAFLD progression. Mutual interaction between endoplasmic reticulum stress (ERS) and oxidative stress play important roles in NAFLD pathogenesis. Notably, mitochondria-associated membranes (MAMs) act as a structural bridges for functional clustering of molecules, particularly for Ca 2+ , lipids, and reactive oxygen species (ROS) exchange. Previous studies have examined the crucial roles of ERS and ROS in NAFLD and have shown that MAM structural and functional integrity determines normal ER-mitochondria communication. Upon disruption of MAM integrity, miscommunication directly or indirectly causes imbalances in Ca2+ homeostasis and increases ERS and oxidative stress. Here, we emphasize the involvement of MAMs in glucose and lipid metabolism, chronic inflammation and insulin resistance in NAFLD and summarize MAM-targeting drugs and compounds, most of which achieve their therapeutic or ameliorative effects on NAFLD by improving MAM integrity. Therefore, targeting MAMs may be a viable strategy for NAFLD treatment. This review provides new ideas and key points for basic NAFLD research and drug development centred on mitochondria and the endoplasmic reticulum.

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MTP genetic variants associated with non-alcoholic fatty liver in metabolic syndrome patients

Cited by 15 publications

References 49 publications

Pathophysiological, Molecular and Therapeutic Issues of Nonalcoholic Fatty Liver Disease: An Overview

Pathophysiological, Molecular and Therapeutic Issues of Nonalcoholic Fatty Liver Disease: An Overview

The association between SNPs rs1800591 and rs3816873 of the MTTP gene and nonalcoholic fatty liver disease: A meta-analysis

Mutual interaction between endoplasmic reticulum and mitochondria in nonalcoholic fatty liver disease

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