Genetics of Non-Alcoholic Fatty Liver and Cardiovascular Disease: Implications for Therapy?

被引：23

作者：

Chandrasekharan, Karthik ^{[1
]}

Alazawi, William ^{[1
]}

机构：

[1] Queen Mary Univ London, Barts Liver Ctr, Blizard Inst, London, England

来源：

FRONTIERS IN PHARMACOLOGY | 2020年 / 10卷

关键词：

non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; cardiovascular disease; genome wide association studies; therapeutics; GCKR RS780094 POLYMORPHISM; GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; FASTING PLASMA-GLUCOSE; HEPATOCELLULAR-CARCINOMA; CONFERS SUSCEPTIBILITY; HISTOLOGICAL SEVERITY; PNPLA3; RISK; VARIANT;

D O I：

10.3389/fphar.2019.01413

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. The most common cause of mortality in NAFLD is cardiovascular disease (CVD), and a key of focus in drug development is to discover therapies that target both liver injury and CVD risk. NAFLD and CVD are complex disease spectra with complex heritability patterns. Nevertheless, genome wide association studies and meta-analyses of these have identified genetic loci that are associated with increased risk of relevant pathological features of disease or clinical endpoints. This review focuses on the genetic risk loci identified in the NAFLD spectrum and asks whether any of these are also risk factors for CVD. Surprisingly, given the shared co-morbidities and risk factors, little robust evidence exists that NAFLD and CVD share genetic risk. Despite this, therapeutic intervention that targets both liver disease and CVD remains an important clinical need and a major focus for pharmaceutical development.

引用

页数：7

共 85 条

[1] The SOD2 C47T polymorphism influences NAFLD fibrosis severity: Evidence from case-control and intra-familial allele association studies [J].

Al-Serri, Ahmad ;

Anstee, Quentin M. ;

Valenti, Luca ;

Nobili, Valerio ;

Leathart, Julian B. S. ;

Dongiovanni, Paola ;

Patch, Julia ;

Fracanzani, Anna ;

Fargion, Silvia ;

Day, Christopher P. ;

Daly, Ann K. .

JOURNAL OF HEPATOLOGY, 2012, 56 (02) :448-454

[2] Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults [J].

Alexander, Myriam ;

Loomis, A. Katrina ;

van der Lei, Johan ;

Duarte-Salles, Talita ;

Prieto-Alhambra, Daniel ;

Ansell, David ;

Pasqua, Alessandro ;

Lapi, Francesco ;

Rijnbeek, Peter ;

Mosseveld, Mees ;

Avillach, Paul ;

Egger, Peter ;

Dhalwani, Nafeesa N. ;

Kendrick, Stuart ;

Celis-Morales, Carlos ;

Waterworth, Dawn M. ;

Alazawi, William ;

Sattar, Naveed .

BMJ-BRITISH MEDICAL JOURNAL, 2019, 367

[3] Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts [J].

Alexander, Myriam ;

Loomis, A. Katrina ;

van der Lei, Johan ;

Duarte-Salles, Talita ;

Prieto-Alhambra, Daniel ;

Ansell, David ;

Pasqua, Alessandro ;

Lapi, Francesco ;

Rijnbeek, Peter ;

Mosseveld, Mees ;

Waterworth, Dawn M. ;

Kendrick, Stuart ;

Sattar, Naveed ;

Alazawi, William .

BMC MEDICINE, 2019, 17 (1)

[4] Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease [J].

Angulo, Paul ;

Kleiner, David E. ;

Dam-Larsen, Sanne ;

Adams, Leon A. ;

Bjornsson, Einar S. ;

Charatcharoenwitthaya, Phunchai ;

Mills, Peter R. ;

Keach, Jill C. ;

Lafferty, Heather D. ;

Stahler, Alisha ;

Haflidadottir, Svanhildur ;

Bendtsen, Flemming .

GASTROENTEROLOGY, 2015, 149 (02) :389-+

[5] The genetics of NAFLD [J].

Anstee, Quentin M. ;

Day, Christopher P. .

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2013, 10 (11) :645-655

[6] The PNPLA3 Variant Associated With Fatty Liver Disease (I148M) Accumulates on Lipid Droplets by Evading Ubiquitylation [J].

BasuRay, Soumik ;

Smagris, Eriks ;

Cohen, Jonathan C. ;

Hobbs, Helen H. .

HEPATOLOGY, 2017, 66 (04) :1111-1124

[7] The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver [J].

Beer, Nicola L. ;

Tribble, Nicholas D. ;

McCulloch, Laura J. ;

Roos, Charlotta ;

Johnson, Paul R. V. ;

Orho-Melander, Marju ;

Gloyn, Anna L. .

HUMAN MOLECULAR GENETICS, 2009, 18 (21) :4081-4088

[8] Relationship Between Nonalcoholic Fatty Liver Disease Susceptibility Genes and Coronary Artery Disease [J].

Brouwers, Martijn C. G. J. ;

Simons, Nynke ;

Stehouwer, Coen D. A. ;

Koek, Ger H. ;

Schaper, Nicolaas C. ;

Isaacs, Aaron .

HEPATOLOGY COMMUNICATIONS, 2019, 3 (04) :587-596

[9] A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis [J].

Buch, Stephan ;

Stickel, Felix ;

Trepo, Eric ;

Way, Michael ;

Herrmann, Alexander ;

Nischalke, Hans Dieter ;

Brosch, Mario ;

Rosendahl, Jonas ;

Berg, Thomas ;

Ridinger, Monika ;

Rietschel, Marcella ;

McQuillin, Andrew ;

Frank, Josef ;

Kiefer, Falk ;

Schreiber, Stefan ;

Lieb, Wolfgang ;

Soyka, Michael ;

Semmo, Nasser ;

Aigner, Elmar ;

Datz, Christian ;

Schmelz, Renate ;

Brueckner, Stefan ;

Zeissig, Sebastian ;

Stephan, Anna-Magdalena ;

Wodarz, Norbert ;

Deviere, Jacques ;

Clumeck, Nicolas ;

Sarrazin, Christoph ;

Lammert, Frank ;

Gustot, Thierry ;

Deltenre, Pierre ;

Voelzke, Henry ;

Lerch, Markus M. ;

Mayerle, Julia ;

Eyer, Florian ;

Schafmayer, Clemens ;

Cichon, Sven ;

Noethen, Markus M. ;

Nothnagel, Michael ;

Ellinghaus, David ;

Huse, Klaus ;

Franke, Andre ;

Zopf, Steffen ;

Hellerbrand, Claus ;

Moreno, Christophe ;

Franchimont, Denis ;

Morgan, Marsha Y. ;

Hampe, Jochen .

NATURE GENETICS, 2015, 47 (12) :1443-+

[10] The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association [J].

Chalasani, Naga ;

Younossi, Zobair ;

Lavine, Joel E. ;

Diehl, Anna Mae ;

Brunt, Elizabeth M. ;

Cusi, Kenneth ;

Charlton, Michael ;

Sanyal, Arun J. .

HEPATOLOGY, 2012, 55 (06) :2005-2023

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