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Potential clinical variants detected in mitochondrial DNA D-loop hypervariable region I of patients with non-alcoholic steatohepatitis

  • Burcu Hasturk
  • Yusuf Yilmaz
  • Fatih ErenEmail author
Original article



Non-alcoholic steatohepatitis (NASH) is a mitochondrial disease. However, the underlying role of mitochondrial genetics has not yet been completely elucidated. Evaluation of D-loop nucleotide variations with respect to statistical significance and clinical data distribution.


Genomic DNAs were extracted from the peripheral blood samples of patients with biopsy-proven 150 NASH as well as from 150 healthy individuals to explore the functional D-loop region responsible for the replication and transcription of the mitochondrial genome. DNA sequencing by capillary electrophoresis analysis was performed for the D-loop region of mitochondrial DNA containing the hypervariable region I, and restriction fragment length polymorphism with MnlI analysis was performed for the m.16189 T/C D-loop variant.


The m.A16318C variant was detected only in patients with NASH and approached significance level. Based on clinical data, six variants associated with histological subgroups of NASH and NASH-complicated diseases were identified. In patients with NASH, the m.16129 AA genotype was associated with advanced-stage fibrosis; the m.16249 CC genotype was associated with advanced lobular inflammation and advanced-stage histological steatosis; the m.16296 TT genotype was associated with hypothyroidism; the m.16163 GG and m.16294 TT genotypes were associated with metabolic syndrome; and the m.16256 TT+CT genotypes were associated with type II diabetes. In patients with NASH, microRNAs were estimated by targeting the significant variants identified in this study.


These findings suggest that NASH may be associated with D-loop nucleotide variations and that microRNA-based in vitro and/or in vivo studies may be developed by targeting the D-loop variants.


D-loop MicroRNA target prediction Mitochondrial DNA Non-alcoholic steatohepatitis Non-alcoholic fatty liver disease Polymorphism 



We thank all volunteers who agreed to participate in the study. The authors are grateful to Dr. Ruslan Asadov for performing liver biopsies and Prof. Dr. Cigdem Ataizi Celikel for the histological evaluation of liver specimens.

Funding information

This study was financially supported by the Scientific Research Project Coordination Unit to Marmara University, Istanbul, Turkey (Grant No. SAG-C-YLP-131016-0439; Grant No. SAG-D-090517-0263).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the local ethics committee (Marmara University School of Medicine, Istanbul, Turkey; protocol no. 09.2016.097; approval date, 29 January 2016).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

42000_2019_137_MOESM1_ESM.pdf (154 kb)
ESM 1 (PDF 153 kb)


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Copyright information

© Hellenic Endocrine Society 2019

Authors and Affiliations

  1. 1.Department of Medical Biology and Genetics, Institute of Health SciencesMarmara UniversityIstanbulTurkey
  2. 2.Department of Gastroenterology, School of MedicineMarmara UniversityIstanbulTurkey
  3. 3.Institute of GastroenterologyMarmara UniversityIstanbulTurkey
  4. 4.Department of Medical Biology, School of MedicineMarmara UniversityIstanbulTurkey

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