Investigation of PNPLA3 and IL28B Genotypes on Diabetes and Obesity After Liver Transplantation: Insight Into Mechanisms of Disease

Watt, Kymberly D.; Dierkhising, Ross A.; Fan, Chun; Heimbach, Julie K.; Tillman, Hans L.; Goldstein, David; Thompson, Amber; Krishnan, Anuradha; Charlton, Michael

doi:10.1111/ajt.12355

Cited by 46 publications

(21 citation statements)

References 31 publications

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“…This hypothesis has been confirmed by a recent study demonstrating that recipient’s but not donor’s PNPLA3 genotype was associated with increased risk of steatosis, supporting the role of extrahepatic (adipocyte) PNPLA3 activity in liver fat accumulation [116]. These results are reinforced by the study of Watt et al , that demonstrated that recipient but not the donor PNPLA3 genotype is associated with the risk of obesity and type 2 diabetes after LT [117]. …”

Section: After Liver Transplantationmentioning

confidence: 67%

NAFLD and liver transplantation: Current burden and expected challenges

Pais

Barritt

Calmus

et al. 2016

Journal of Hepatology

370

315

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Summary Because of global epidemics of obesity and type 2 diabetes, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing both in Europe and the United States, becoming one of the most frequent causes of chronic liver disease and predictably, one of the leading causes of liver transplantation both for end-stage liver disease and hepatocellular carcinoma. For most transplant teams around the world this will raise many challenges in terms of preand post-transplant management. Here we review the multifaceted impact of NAFLD on liver transplantation and will discuss: (1) NAFLD as a frequent cause of cryptogenic cirrhosis, end-stage chronic liver disease, and hepatocellular carcinoma; (2) prevalence of NAFLD as an indication for liver transplantation both in Europe and the United States; (3) the impact of NAFLD on the donor pool; (4) the access of NAFLD patients to liver transplantation and their management on the waiting list in regard to metabolic, renal and vascular comorbidities; (5) the prevalence and consequences of post-transplant metabolic syndrome, recurrent and de novo NAFLD; (6) the alternative management and therapeutic options to improve the long-term outcomes with particular emphasis on the correction and control of metabolic comorbidities.

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Section: After Liver Transplantationmentioning

confidence: 67%

NAFLD and liver transplantation: Current burden and expected challenges

Pais

Barritt

Calmus

et al. 2016

Journal of Hepatology

370

315

View full text Add to dashboard Cite

show abstract

“…A recent transplant research revealed that PNPLA3 of non-CC genotype is associated with post-transplant obesity but not independently with diabetes. Furthermore, the donor genotypes were not associated with obesity or diabetes [99] . This research highlighted the potential of peripheral mechanism for insulin resistance and could reflect a multi-factorial gene involvement in NAFLD.…”

Section: Genes That Affect Lipolysismentioning

confidence: 89%

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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“…Petit et al demonstrated that liver fibrosis was associated with this PNPLA3 I148M carriage in individuals with type 2 diabetes [12] . There may be an increased risk of the progression of liver disease in individuals with the derived GG alleles because patients who needed a liver transplant were twice as likely to have this polymorphism [13] . The carriage of I148M is associated with the development and severity of NAFLD likely by the mechanism of reduced TG catabolism [14] .…”

Section: Discussionmentioning

confidence: 99%

NAFLD Susceptibility Genes and Their Association with Type 2 Diabetes and Obesity in a New Mexico Population

Garner¹,

Conn²,

Cohen³

et al. 2015

JDO

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Objective Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) that increase the risk of developing non-alcoholic fatty liver disease (NAFLD). One purpose of this study was to determine the frequencies of NAFLD susceptibility SNPs in a non-Hispanic white and Hispanic population who attended a clinic in northeast Albuquerque, NM. Another goal was to determine associations with selected indicators in this New Mexican population. Methods This cohort study involving 168 volunteer subjects in the NM population (88 non-Hispanic whites, 63 Hispanics, 4 Native Americans, 11 Asian Americans, 2 unreported ethnicity). Eight SNPs within 6 NAFLD susceptibility genes including PNPLA3 (rs738409), LYPLAL1 (rs12137855), APOC3 (rs2854116, rs2854117), GCKR (rs780094, rs741038), FABP2 (rs1799883), PEMT (rs7946) were analyzed by genotyping using the TaqMan genotyping assay (Applied Biosystems, Foster City, CA). Statistical analyses were carried out using statistical package SAS 9.3. Results The NAFLD allele frequencies were similar in non-Hispanic whites and Hispanics except for PNPLA3 (rs738409), FABP2 (rs1799883), and PEMT (rs7946). Eight SNPs in 5 NAFLD susceptibility genes were significantly associated OR marginally associated with selected indicators for NAFLD, metabolic syndrome, overweight, obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia. No SNPs were significantly associated with the same indicator in both the non-Hispanic white and Hispanic groups. Conclusions In this population of non-Hispanic whites and Hispanics, there were only heterozygotes for the APOC3 derived alle le whereas for all other genes tested, both heterozygotes and homozygotes were found. Associations of alleles with indicators of chronic disease were different in non-Hispanic whites compared to Hispanics.

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Investigation of PNPLA3 and IL28B Genotypes on Diabetes and Obesity After Liver Transplantation: Insight Into Mechanisms of Disease

Cited by 46 publications

References 31 publications

NAFLD and liver transplantation: Current burden and expected challenges

NAFLD and liver transplantation: Current burden and expected challenges

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

NAFLD Susceptibility Genes and Their Association with Type 2 Diabetes and Obesity in a New Mexico Population

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