Journal of Assisted Reproduction and Genetics

, Volume 35, Issue 3, pp 533–538 | Cite as

Polymorphisms of mitochondrial DNA control region are associated to endometriosis

  • Marina Paula Andres
  • Mari Maki Siria Godoy Cardena
  • Cintia Fridman
  • Sergio Podgaec



Polymorphisms in the control region of mitochondrial DNA (mtDNA) can affect generation of reactive oxygen species and impact in the pathogenesis of endometriosis. This study investigated the association of mtDNA polymorphisms with endometriosis.


Patients were divided in two groups: endometriosis (n = 90) and control (n = 92). Inclusion criteria were as follows: women between 18 and 50 years, with histological diagnosis and surgical staging of endometriosis (endometriosis group) or undergoing gynecological surgery for tubal ligation, leiomyoma, or ovarian cysts, with no evidence of endometriosis (control group). DNA extraction was performed from peripheral blood. Sanger sequencing of mtDNA control region was performed, and polymorphisms were determined comparing the sequences obtained with the Cambridge Reference Sequence.


The frequency of polymorphisms T16217C (14.4 and 5.4% of endometriosis and control group, respectively; p = 0.049) and G499A (13.3 vs. 4.3%; p = 0.038) was higher in the endometriosis group, while T146C (32.6 vs. 18.9%; p = 0.042) and 573.2C (5.6 vs. 29.3%; p < 0.001) were lower. No difference was observed in haplogroups between groups.


mtDNA polymorphisms T16217C and G499A were associated with endometriosis, while T416C and 573.2C were shown to be associated with an absence of disease.


Endometriosis Mitochondrial DNA Polymorphism Brazilian population Medical genetics 


Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest.

Supplementary material

10815_2017_1082_MOESM1_ESM.docx (54 kb)
ESM 1 (DOCX 54 kb)


  1. 1.
    Prescott J, Farland LV, Tobias DK, Gaskins AJ, Spiegelman D, Chavarro JE, et al. A prospective cohort study of endometriosis and subsequent risk of infertility. Hum Reprod. 2016;31(7):1475–82.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Kobayashi H, Imanaka S, Nakamura H, Tsuji A. Understanding the role of epigenomic, genomic and genetic alterations in the development of endometriosis (review). Mol Med Rep. 2014;9(5):1483–505.CrossRefPubMedGoogle Scholar
  3. 3.
    Turkyilmaz E, Yildirim M, Cendek BD, Baran P, Alisik M, Dalgaci F, et al. Evaluation of oxidative stress markers and intra-extracellular antioxidant activities in patients with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2016;199:164–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Govatati S, Deenadayal M, Shivaji S, Bhanoori M. Mitochondrial displacement loop alterations are associated with endometriosis. Fertil Steril. 2013;99(7):1980–6.e9.CrossRefPubMedGoogle Scholar
  5. 5.
    Srinivasan S, Guha M, Kashina A, Avadhani NG. Mitochondrial dysfunction and mitochondrial dynamics—the cancer connection. Biochim Biophys Acta. 2017.Google Scholar
  6. 6.
    Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet. 1999;23(2):147.CrossRefPubMedGoogle Scholar
  7. 7.
    Kao SH, Huang HC, Hsieh RH, Chen SC, Tsai MC, Tzeng CR. Oxidative damage and mitochondrial DNA mutations with endometriosis. Ann N Y Acad Sci. 2005;1042:186–94.CrossRefPubMedGoogle Scholar
  8. 8.
    Shu J, Xing L, Ding G, Luo Q, Liu X, Yan Q, et al. The effect of peritoneal fluid from patients with endometriosis on mitochondrial function and development of early mouse embryos. PLoS One. 2013;8(12):e82334.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cho S, Lee YM, Choi YS, Yang HI, Jeon YE, Lee KE, et al. Mitochondria DNA polymorphisms are associated with susceptibility to endometriosis. DNA Cell Biol. 2012;31(3):317–22.CrossRefPubMedGoogle Scholar
  10. 10.
    Govatati S, Tipirisetti NR, Perugu S, Kodati VL, Deenadayal M, Satti V, et al. Mitochondrial genome variations in advanced stage endometriosis: a study in South Indian population. PLoS One. 2012;7(7):e40668.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Cardena MM, Ribeiro-Dos-Santos A, Santos S, Mansur AJ, Pereira AC, Fridman C. Assessment of the relationship between self-declared ethnicity, mitochondrial haplogroups and genomic ancestry in Brazilian individuals. PLoS One. 2013;8(4):e62005.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kirkwood B, Sterne J. Essential medical statistics. 2nd ed. Massachusetts: Blackwell Science; 2006.Google Scholar
  13. 13.
    Wang C, Zhang F, Fan H, Peng L, Zhang R, Liu S, et al. Sequence polymorphisms of mitochondrial D-loop and hepatocellular carcinoma outcome. Biochem Biophys Res Commun. 2011;406(3):493–6.CrossRefPubMedGoogle Scholar
  14. 14.
    American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67(5):817–21.Google Scholar
  15. 15.
    Carracedo A, Bär W, Lincoln P, Mayr W, Morling N, Olaisen B, et al. DNA commission of the international society for forensic genetics: guidelines for mitochondrial DNA typing. Forensic Sci Int. 2000;110(2):79–85.CrossRefPubMedGoogle Scholar
  16. 16.
    van Oven M, Kayser M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat. 2009;30(2):E386–94.CrossRefPubMedGoogle Scholar
  17. 17.
    Gómez-Durán A, Pacheu-Grau D, Martínez-Romero I, López-Gallardo E, López-Pérez MJ, Montoya J, et al. Oxidative phosphorylation differences between mitochondrial DNA haplogroups modify the risk of Leber’s hereditary optic neuropathy. Biochim Biophys Acta. 2012;1822(8):1216–22.CrossRefPubMedGoogle Scholar
  18. 18.
    Bellelis P, Dias JA, Podgaec S, Gonzales M, Baracat EC, Abrão MS. Epidemiological and clinical aspects of pelvic endometriosis—a case series. Rev Assoc Med Bras (1992). 2010;56(4):467–71.CrossRefGoogle Scholar
  19. 19.
    Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D'Hooghe T, De Bie B, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29(3):400–12.CrossRefPubMedGoogle Scholar
  20. 20.
    Wallace DC. Mitochondrial DNA variation in human radiation and disease. Cell. 2015;163(1):33–8.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Liou CW, Chen JB, Tiao MM, Weng SW, Huang TL, Chuang JH, et al. Mitochondrial DNA coding and control region variants as genetic risk factors for type 2 diabetes. Diabetes. 2012;61(10):2642–51.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Tuppen HA, Hogan VE, He L, Blakely EL, Worgan L, Al-Dosary M, et al. The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families. Brain. 2010;133(10):2952–63.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Fan H, Wang C, Guo Z. Single nucleotide polymorphisms in the mitochondrial displacement loop and age at onset of non-Hodgkin lymphoma. Onco Targets Ther. 2013;6:1041–5.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Stewart JB, Chinnery PF. The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease. Nat Rev Genet. 2015;16(9):530–42.CrossRefPubMedGoogle Scholar
  25. 25.
    Paneto GG, Köhnemann S, Martins JA, Cicarelli RM, Pfeiffer H. A single multiplex PCR and SNaPshot minisequencing reaction of 42 SNPs to classify admixture populations into mitochondrial DNA haplogroups. Mitochondrion. 2011;11(2):296–302.CrossRefPubMedGoogle Scholar
  26. 26.
    Feio-Dos-Santos AC, Carvalho BM, Batista dos Santos SE, Ribeiro-dos-Santos AK. Nucleotide variability of HV-I in admixed population of the Brazilian Amazon region. Forensic Sci Int. 2006;164(2–3):276–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Fridman C, Gonzalez RS, Pereira AC, Cardena MM. Haplotype diversity in mitochondrial DNA hypervariable region in a population of southeastern Brazil. Int J Legal Med. 2014;128(4):589–93.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Marina Paula Andres
    • 1
  • Mari Maki Siria Godoy Cardena
    • 2
  • Cintia Fridman
    • 2
  • Sergio Podgaec
    • 1
    • 3
  1. 1.Gynecologic Division, Hospital das Clinicas HCFMUSP, Faculdade de MedicinaUniversidade de Sao PauloSao PauloBrazil
  2. 2.Department of Legal Medicine, Ethics and Occupational Health, Faculdade de Medicina FMUSPUniversidade de Sao PauloSao PauloBrazil
  3. 3.Jewish Teaching and Research InstituteHospital Israelita Albert EinsteinSão PauloBrazil

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