Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jan 8:10:1413.
doi: 10.3389/fphar.2019.01413. eCollection 2019.

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

Karthik Chandrasekharan  1 , William Alazawi  1
Affiliations
Review

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

Karthik Chandrasekharan et al. Front Pharmacol. .

Abstract

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.

Keywords: cardiovascular disease; genome wide association studies; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; therapeutics.

PubMed Disclaimer

References

    1. Alexander M., Loomis A. K., Lei J. V. D., Duarte-Salles T., Prieto-Alhambra D., Ansell D., et al. (2019. a). Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults. BMJ 367, l5367. 10.1136/bmj.l5367 - DOI - PMC - PubMed
    1. Alexander M., Loomis A. K., van der Lei J., Duarte-Salles T., Prieto-Alhambra D., Ansell D., et al. (2019. b). 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. BMC Med. 17, 95. 10.1186/s12916-019-1321-x - DOI - PMC - PubMed
    1. Al-Serri A., Anstee Q. M., Valenti L., Nobili V., Leathart J. B. S., Dongiovanni P., et al. (2012). The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies. J. Hepatol. 56, 448–454. 10.1016/j.jhep.2011.05.029 - DOI - PubMed
    1. Angulo P., Kleiner D. E., Dam-Larsen S., Adams L. A., Bjornsson E. S., Charatcharoenwitthaya P., et al. (2015). Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 149, 389–397. e10. 10.1053/j.gastro.2015.04.043 - DOI - PMC - PubMed
    1. Anstee Q. M., Day C. P. (2013). The genetics of NAFLD. Nat. Rev. Gastroenterol. Hepatol. 10, 645–655. 10.1038/nrgastro.2013.182 - DOI - PubMed

LinkOut - more resources