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
. 2016 Sep 5;17(1):63.
doi: 10.1186/s12881-016-0324-0.

The role of mitochondrial genomics in patients with non-alcoholic steatohepatitis (NASH)

Rohini Mehta  1 , Kianoush Jeiran  2 , Aaron B Koenig  1 , Munkzhul Otgonsuren  1 , Zachary Goodman  1 , Ancha Baranova  2 , Zobair Younossi  3   4
Affiliations

The role of mitochondrial genomics in patients with non-alcoholic steatohepatitis (NASH)

Rohini Mehta et al. BMC Med Genet. .

Abstract

Background: Visceral obesity and metabolic syndrome are commonly associated with non-alcoholic fatty liver disease (NAFLD). The progression of steatosis to NASH depends on a number of metabolic and patient-related factors. The mechanisms of genetic predisposition towards the development of NASH and related fibrosis remain unclear. In this study, our aim was to utilize mitotyping and identify mitochondrial haplotypes that may be associated with NAFLD.

Methods: We examined mitochondrial haplotypes along with patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 genotype to determine their association with NAFLD phenotypes. Whole blood samples were obtained from 341 patients (BMI > 35) undergoing weight reduction surgery after written consent. Liver biopsies were centrally reviewed by a single pathologist based on predetermined pathologic protocol (41.9 % Non-NASH NAFLD, 30.4 % NASH, 27.5 % controls). A 1,122 bp of the mitochondrial control loop was sequenced for each sample and classified into haplogroups.

Results: The presence of haplogroup L exhibits protection against the development of NASH and pericellular fibrosis. The alleles of PNPLA3 locus showed differential distribution in cohorts with NAFLD, NASH and pericellular fibrosis. Heterozygosity at this locus is independently associated with higher risk of having NASH and pericellular fibrosis.

Conclusion: Mitochondrial genetics play an important role in NASH probably by modulation of oxidative stress and the efficiency of oxidative phosphorylation.

Keywords: Ethnicity; Hepatic fibrosis; Obesity; PNPLA3 rs738409.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
The prevalence of PNPLA3 rs738409 variant in NASH, Non-NASH NAFLD and Normal Liver Histology cohorts (p < 0.05 significant). * Significant pair-wise comparison between controls with normal liver histology and NASH; + Significant pair-wise comparison between Non-NASH NAFLD and NASH; x Significant pair-wise comparison between controls with normal liver histology and Non-NASH NAFLD
Fig. 2
Fig. 2
Haplogroup distribution by self-identified ethnicity in our study population. European lineages: H, T, U, V, X, K, N, I, J, HV, W; African Lineages: L, L1, L2, L3, L3; Asian/American Indian: A, B, F, macro-haplogroup M (C, D, E, and G), X
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Erickson SK. Nonalcoholic fatty liver disease. J Lipid Res. 2009;50(Suppl):S412–S416. - PMC - PubMed
    1. Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol. 2010;5:145–171. doi: 10.1146/annurev-pathol-121808-102132. - DOI - PubMed
    1. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34:274–285. doi: 10.1111/j.1365-2036.2011.04724.x. - DOI - PubMed
    1. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. 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. Hepatology. 2012;55:2005–2023. doi: 10.1002/hep.25762. - DOI - PubMed
    1. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatol Baltim Md. 2003;37:1202–1219. doi: 10.1053/jhep.2003.50193. - DOI - PubMed

Publication types