<scp>I</scp>mpact of leptin receptor gene variants on risk of non‐alcoholic fatty liver disease and its interaction with adiponutrin gene

Zain, Sharifuddin M.; Mohamed, Zahurin; Mahadeva, Sanjiv; Cheah, Phaik Leng; Rampal, Sanjay; Chin, Kin-Fah; Mahfudz, Anis Shafina; Basu, Roma Choudhury; Tan, Hwa Li; Mohamed, Rosmawati

doi:10.1111/jgh.12104

Cited by 36 publications

(27 citation statements)

References 38 publications

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“…Recently, an association between variants of LEPR and PNPLA3 has been reported. The interactions between LEPR and PNPLA3 genes showed an increased risk of NAFLD compared to either gene alone [139] .…”

Section: Genes That Affect Adipokinesmentioning

confidence: 99%

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Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

Lim

Dillon

Miller

2014

WJG

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Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patientdisease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) antiinflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production. Key words: Non-alcoholic fatty liver disease; Proteomics; Genomics; Metabolic syndrome; Pathophysiology Core tip: Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder in Western populations. NAFLD can occur as a spectrum diseases, from simple steatosis, to non-alcoholic steatohepatitis characterised by hepatocellular injury and inflammation, to cirrhosis and hepatocellular carcinoma. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. This review highlighted several functional proteins and genetic polymoprhisms; particular those involved in insulin resistance, triglycerides metabolism and hepatic inflammation. It is hoped that this review will offer further insights into the pathophysiology of NAFLD.

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Section: Genes That Affect Adipokinesmentioning

confidence: 99%

“…Raises the possibility and association of antiinflammatory effect in NAFLD progression and oncological disease LEP and LEPR Zain et al [139] 2013 Demonstrated an association between variants of LEPR and PNPLA3…”

Section: De Novo Lipogenesis Plays a Role In Nafldmentioning

confidence: 99%

Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

Lim

Dillon

Miller

2014

WJG

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“…Furthermore, by mediating lipid metabolism and insulin sensitivity, the LepRb G2057A SNP is conducive to the onset of NAFLD (27). However, the LepRb Arg233Gln polymorphism has been indicated in relation to lower cholesterol, low-density lipoprotein (LDL) levels and fibrosis score in NAFLD (28). Patients carrying the SNPs of LepRb (rs1137100) with patatin-like phospholipase domain containing 3 (rs738409) have ~three-fold risk of suffering from NAFLD than those carrying either SNP, both genes are correlatively upregulated in the absence of excess lipids (28).…”

Section: Leptin and Leptin Receptor (Leprb)mentioning

confidence: 99%

“…However, the LepRb Arg233Gln polymorphism has been indicated in relation to lower cholesterol, low-density lipoprotein (LDL) levels and fibrosis score in NAFLD (28). Patients carrying the SNPs of LepRb (rs1137100) with patatin-like phospholipase domain containing 3 (rs738409) have ~three-fold risk of suffering from NAFLD than those carrying either SNP, both genes are correlatively upregulated in the absence of excess lipids (28). Leptin inhibits steatosis via downregulating stearoyl-CoA desaturase-1 and sterol regulatory element binding protein (SREBP) 1c.…”

Section: Leptin and Leptin Receptor (Leprb)mentioning

confidence: 99%

Development of gene polymorphisms in meditators of nonalcoholic fatty liver disease

Wang

Gong

2017

Biomedical Reports

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Abstract. Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, the morbidity of which closely correlates with diversity of ethnicity, minority, family and location. Its histology spans from simple steatosis, to nonalcoholic steatohepatitis, which ultimately results in fibrosis, cirrhosis and hepatocellular carcinoma. The accelerating prevalence of NAFLD is due to an incremental incidence of metabolic syndrome that is distinguished by dyslipidemia, glucose impairment, obesity, excessive oxidative stress and adipocytokine impairment. Additionally, the pathogenesis of NAFLD is thought to be a multifactorial and complicated disease associated with lifestyle habits, nutritional factors and genetics. However, the pathogenesis and underlying mechanism in the development of NAFLD caused by genetics remains unclear. People have been increasingly emphasizing on the relationship between NAFLD and gene polymorphisms in recent years, with the aim of having a comprehensive elucidation of associated gene polymorphisms influencing the pathogenesis of the disease. In the current article, the authors attempted to critically summarize the most recently identified gene polymorphisms from the facets of glucose metabolism, fatty acid metabolism, oxidative stress and related cytokines in NAFLD that contribute to promoting the progression of the disease.

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“…The polymorphism of LEPR 3057G > A (rs1805096) may responsible to the onset of NAFLD by regulating lipid metabolism and altering insulin sensitivity [190]. LEPR rs1137100 is associated with increased risk of NAFLD and NASH [191].…”

Section: Gene Therapymentioning

confidence: 99%

Type 2 Diabetes and Developmental Origin of Non-Alcohol Fatty Liver Disease and Future Directions of Treatment

Hi¹,

Ea²

2016

Clin Exp Pharmacol

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Non-alcohol fatty liver disease is a large public health problem developed earlier during intrauterine life as a result of gestational or type 2 diabetes. The disease is associated with altered liver enzymes, lipid accumulation and hepatic steatosis due to hepatic de novo lipogenesis. Multiple factors are associated in the development of the disease such as peroxisome proliferator-activated receptor-γ co-activator, B-cell dysfunction and abnormal metabolism of mitochondria, lysosomes, rough endoplasmic reticulum and Golgi complex. These factors are discussed in details. Different approaches of drug-treatment, phyto-& gene therapy are illustrated. Role of type 2 or gestational diabetes on developmental origin of fatty liver. The interrelation-ship between type 2 diabetes and obesity and fetus's liver. Role of cytoplasmic organelles in de novo lipogenesis, inflammation, and hepatocyte cell death. Future direction of drug-treatment, phyto-and gene-therapy.

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Impact of leptin receptor gene variants on risk of non‐alcoholic fatty liver disease and its interaction with adiponutrin gene

Cited by 36 publications

References 38 publications

Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

Development of gene polymorphisms in meditators of nonalcoholic fatty liver disease

Type 2 Diabetes and Developmental Origin of Non-Alcohol Fatty Liver Disease and Future Directions of Treatment

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