Detection of Somatic Mutations and Germline Polymorphisms in Mitochondrial DNA of Uterine Fibroids Patients

摘要

To identify the role of mitochondrial DNA (mtDNA) mutations in uterine fibroids patients, genomic DNA isolated from paired myometrium and fibroid tissues was screened for mutations. The present study represents the first investigation to report that 10.4% of uterine fibroids cases had either mtDNA mutations or polymorphisms or both. Among the 14 mitochondrial sequence variants identified, seven are somatic mutations (A3327C, G3352A, G3376A, G3380A, G3421A, T15312G, and C15493G) and the remaining (G3316A, C3342A, C3442T, T10205A, A10188G, A10229C, and A10301T) are gene polymorphisms. Somatic mutations were both homo- and heteroplasmic in nature. Of the seven somatic mutations located in the MTND1 and MTCYB genes, five (71.42%) are nonsynonymous in nature, whereas four (57.14%) of the polymorphisms located in MTND1 and MTND3 genes are found to be nonsynonymous. Sequence variants such as G3380A, G3421A, T15312G, G3376A, and G3316A have been earlier described in different human pathologies, but the remaining are novel ones. Mitochondrial somatic mutations and polymorphisms may predispose women to an earlier onset of degenerative cellular processes, which impair oxidative phosphorylation capacity and thereby promote tu-morigenesis in uterine smooth muscle cells. Detection of mtDNA sequence variations in fibroid patients raises the need for larger case-control studies to screen the whole mitochondrial genome and evaluate as a future diagnostic biomarker in fibroid patients.%Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre, Hyderabad, India,Research Chair of Medical and Molecular Genetics, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia;Department of Genetics, University College of Science, Osmania University, Hyderabad, India,Department of Genetics and Molecular Medicine, Kamineni Hospitals, Hyderabad, India;Department of Genetics, University College of Science, Osmania University, Hyderabad, India,Department of Genetics and Molecular Medicine, Kamineni Hospitals, Hyderabad, India;Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre, Hyderabad, India,Department of Genetics, University College of Science, Osmania University, Hyderabad, India;Department of Genetics, University College of Science, Osmania University, Hyderabad, India;Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre, Hyderabad, India;Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre, Hyderabad, India,Department of Genetics and Molecular Medicine, Kamineni Hospitals, Hyderabad, India;