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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgments

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

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).

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Authors and Affiliations

  1. Department of Medical Biology and Genetics, Institute of Health Sciences, Marmara University, Istanbul, Turkey

    Burcu Hasturk

  2. Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey

    Yusuf Yilmaz

  3. Institute of Gastroenterology, Marmara University, Istanbul, Turkey

    Yusuf Yilmaz & Fatih Eren

  4. Department of Medical Biology, School of Medicine, Marmara University, Maltepe Basibuyuk Yolu Road No: 9/2, 34854, Istanbul, Turkey

    Fatih Eren

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  1. Burcu Hasturk
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Correspondence to Fatih Eren.

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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).

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

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Hasturk, B., Yilmaz, Y. & Eren, F. Potential clinical variants detected in mitochondrial DNA D-loop hypervariable region I of patients with non-alcoholic steatohepatitis. Hormones 18, 463–475 (2019). https://doi.org/10.1007/s42000-019-00137-1

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  • DOI: https://doi.org/10.1007/s42000-019-00137-1

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