Adiponectin polymorphisms and non‐alcoholic fatty liver disease risk: A meta‐analysis

Wang, Jun; Guo, Xufeng; Yu, Shijie; Song, Jia; Zhang, Jixiang; Cao, Zhuo; Wang, Jing; Ji, Mengyao; Dong, Weiguo

doi:10.1111/jgh.12562

Cited by 11 publications

(10 citation statements)

References 41 publications

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“…The literature search resulted in 12 NAFLD susceptibility variants, of which five were selected based on previous GWASs for NAFLD (lysophospholipase‐like 1 [ LYPLAL1 ] , glucokinase regulator, [ GCKR ] , protein phosphatase 1 regulatory subunit 3B [ PPP1R3B ] , PNPLA3, and TM6SF2 ), four from previous GWASs for NAFLD‐related traits combined with at least one case‐control study in NAFLD (tribbles pseudokinase 1 [ TRIB1 ], fatty acid desaturase [ FADS1‐2‐3 ], endoplasmic reticulum lipid raft associated 1–conserved helix‐loop‐helix ubiquitous kinase–CWF19‐like cell cycle control factor 1 [ ERLIN1‐CHUK‐CWF19L1 ] , and membrane bound O‐acyltransferase domain containing 7 [ MBOAT7 ]), and three from case‐control studies in NAFLD that were subsequently confirmed by meta‐analysis (adiponectin, C1Q and collagen domain containing [ ADIPOQ ] , microsomal triglyceride transfer protein [ MTTP ] , and phosphatidylethanolamine N‐methyltransferase [ PEMT ]) (Table ). The tissue expression and global function of the genes presumed to underlie these associations are listed in Supporting Table .…”

Section: Resultsmentioning

confidence: 99%

Relationship Between Nonalcoholic Fatty Liver Disease Susceptibility Genes and Coronary Artery Disease

et al. 2019

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Coronary artery disease (CAD) is the principal cause of death in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to investigate whether NAFLD is causally involved in the pathogenesis of CAD. For this, previously reported NAFLD susceptibility genes were clustered and tested for an association with CAD in the Coronary Artery Disease Genome‐Wide Replication and Meta‐Analysis plus the Coronary Artery Disease Genetics (CARDIoGRAMplusC4D) Consortium data set. The role of plasma lipids as a potential mediator was explored by using data from the Global Lipids Genetics Consortium. Statistical analyses revealed that the combination of 12 NAFLD genes was not associated with CAD in 60,801 CAD cases and 123,504 controls (odds ratio [OR] per NAFLD risk allele , 1.0; 95% confidence interval [CI], 0.99‐1.00). In a subsequent sensitivity analysis, a positive relationship was observed after exclusion of gene variants that are implicated in NAFLD through impaired very low‐density lipoprotein secretion (i.e., microsomal triglyceride transfer protein [ MTTP ] , patatin‐like phospholipase domain containing 3 [ PNPLA3 ] , phosphatidylethanolamine N‐methyltransferase [ PEMT ] , and transmembrane 6 superfamily member 2 [ TM6SF2 ]) (OR, 1.01; 95% CI, 1.00‐1.02). Clustering of the excluded genes showed a significant negative relationship with CAD (OR, 0.97; 95% CI, 0.96‐0.99). A substantial proportion of the observed heterogeneity between the individual NAFLD genes in relation to CAD could be explained by plasma lipids, as reflected by a strong relationship between plasma lipids and CAD risk conferred by the NAFLD susceptibility genes ( r = 0.76; P = 0.004 for low‐density lipoprotein cholesterol). Conclusion: NAFLD susceptibility genes do not cause CAD per se . The relationship between these genes and CAD appears to depend to a large extent on plasma lipids. These observations strongly suggest taking plasma lipids into account when designing a new drug to target NAFLD.

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Section: Resultsmentioning

confidence: 99%

Relationship Between Nonalcoholic Fatty Liver Disease Susceptibility Genes and Coronary Artery Disease

et al. 2019

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“…Both +45 T > G (rs2241766) and −11377C > G (rs577853790) have been shown to be associated with NAFLD in a meta‐analysis, a finding that supports the hypothesis that overlapping genetic backgrounds contribute to both NAFLD and CVD, since the adiponectin +45 T > G genotype has been found to be associated with CVD in a separate meta‐analysis . Increased visceral fat is associated with low adiponectin in adolescence, supporting association with adiponectin action via adiponectin receptor 2 ( ADIPOR2 ) in three independent Finnish cohorts; however, among Asian people, a meta‐analysis suggests that adiponectin variants might be risk factors for NAFLD while the +276G > T variant is protective . Simple steatosis progresses to inflammation with risk for cirrhosis and liver cancer, and is independently associated with increased risk of coronary artery disease .…”

Section: Obesity and Cardiometabolic Risk Phenotypesmentioning

confidence: 88%

“…80 Increased visceral fat is associated with low adiponectin in adolescence, 81 supporting association with adiponectin action via adiponectin receptor 2 (ADIPOR2) in three independent Finnish cohorts; 82 however, among Asian people, a meta-analysis suggests that adiponectin variants might be risk factors for NAFLD while the +276G > T variant is protective. 79 Simple steatosis progresses to inflammation with risk for cirrhosis and liver cancer, 83 and is independently associated with increased risk of coronary artery disease. 84 Large-sized VLDL has been observed in NAFLD in an adolescent population independent of adiposity and insulin resistance, and the nuclear magnetic resonance lipid profile was characterized by small dense LDL and a reduced number of large HDL particles.…”

Section: Ectopic Liver Fatmentioning

confidence: 99%

Obesity genetics and cardiometabolic health: Potential for risk prediction

Sanghera

Bejar

Sharma

et al. 2019

Diabetes Obesity Metabolism

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The increasing burden of obesity worldwide and its effect on cardiovascular disease (CVD) risk is an opportunity for evaluation of preventive approaches. Both obesity and CVD have a genetic background and polymorphisms within genes which enhance expression of variant proteins that influence CVD in obesity. Genome‐based prediction may therefore be a feasible strategy, but the identification of genetically driven risk factors for CVD manifesting as clinically recognized phenotypes is a major challenge. Clusters of such risk factors include hyperglycaemia, hypertension, ectopic liver fat, and inflammation. All involve multiple genetic pathways having complex interactions with variable environmental influences. The factors that make significant contributions to CVD risk include altered carbohydrate homeostasis, ectopic deposition of fat in muscle and liver, and inflammation, with contributions from the gut microbiome. A futuristic model depends on harnessing the predictive power of plausible genetic variants, phenotype reversibility, and effective therapeutic choices based on genotype–phenotype interactions. Inverting disease phenotypes into ideal cardiovascular health metrics could improve genetic and epigenetic assessment, and form the basis of a future model for risk detection and early intervention.

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“…Many candidate genes were reported to be associated with NAFLD risk, such as TNF-α, PNPLA3, APOC3, PPAR-γ and adiponectin [34][35][36][37] . Our previous study 38 performed a meta-analysis to evaluate the association between adiponectin polymorphisms and NAFLD susceptibility and the result suggested that adiponectin +45T>G and −11377C>G polymorphisms might be a risk factor for NAFLD, and +276G>T polymorphism may be a protective factor for NAFLD among Asians. As for APOC3, it is a glycoprotein synthesized mainly in the liver and the intestinal, and plays an essential role in regulating the serum triglyceride levels.…”

Section: Discussionmentioning

confidence: 99%

Association between APOC3 polymorphisms and non-alcoholic fatty liver disease risk: a meta-analysis

Wang¹,

Ye²,

Fei³

2020

Afr H. Sci.

Self Cite

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Background and Aim: The apolipoprotein C3 (APOC3) polymorphism has been reported to predispose to non-alcoholic fatty liver disease (NAFLD). However, the results remain inconclusive. This meta-analysis aimed to provide insights into the association between APOC3 polymorphisms and NAFLD risk. Methods: Studies with terms “NALFD” and “APOC3” were retrieved from PubMed, Web of Science, CNKI and Wan- fang databases up to August 1, 2019. Pooled odds ratio (OR) and 95% confidence interval (95% CI) for the association of APOC3 polymorphisms and NAFLD risk were calculated using fixed and random-effects models. Results: A total of twelve studies from eleven articles were included. Of them, eight studies (1750 cases and 2181 controls) reported the strong association of variant rs2854116 with NAFLD and six studies (1523 cases and 1568 controls) found the association of rs2854117 polymorphism with NAFLD. Overall, a statistically significant association between rs2854116 pol- ymorphism of APOC3 gene and NAFLD risk was found only under dominant model. However, association of rs2854117 polymorphism with NAFLD risk was not detected under all four genetic models. In sub-group analysis of NAFLD subjects based on country, no association among them in China was detected. Besides, four studies analyze the association between the two polymorphisms and clinical characteristics in all subjects or NAFLD patients, and we also failed detect any associa- tion between the wild carriers and variant carriers. Conclusion: The meta-analyses suggests that the rs2854116 polymorphism but not rs2854117 polymorphism in APOC3 gene might be a risk factor for NAFLD among Asians. That is, individuals with CT+CC genotype have higher risk of devel- oping NAFLD. However, studies with sufficient sample size are needed for the further validation. Keywords: Apolipoprotein C3; polymorphism; non-alcoholic fatty liver disease; meta-analysis.

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Adiponectin polymorphisms and non‐alcoholic fatty liver disease risk: A meta‐analysis

Abstract: This meta-analysis suggests that adiponectin +45T>G and -11377C>G polymorphisms might be a risk factor for NAFLD, while +276G>T polymorphism may be a protective factor for NAFLD among Asians.

Cited by 11 publications

References 41 publications

Relationship Between Nonalcoholic Fatty Liver Disease Susceptibility Genes and Coronary Artery Disease

Relationship Between Nonalcoholic Fatty Liver Disease Susceptibility Genes and Coronary Artery Disease

Obesity genetics and cardiometabolic health: Potential for risk prediction

Association between APOC3 polymorphisms and non-alcoholic fatty liver disease risk: a meta-analysis

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