BMC Medical Genetics

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

Rohini Mehta,
Kianoush Jeiran,
Aaron B. Koenig,
Munkzhul Otgonsuren,
Zachary Goodman,
Ancha Baranova and
Zobair YounossiEmail author

BMC Medical GeneticsBMC series – open, inclusive and trusted201617:63

DOI: 10.1186/s12881-016-0324-0

Received: 25 June 2016

Accepted: 20 August 2016

Published: 5 September 2016

Open Peer Review reports

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.