Abstract | BACKGROUND: METHODOLOGY: We sequenced the entire mitochondrial genome of analogous ectopic and eutopic endometrial tissues along with blood samples from 32 advanced stage endometriosis patients to analyze the role of somatic and germ-line mtDNA variations in pathogenesis of endometriosis. All ectopic tissues were screened for tumor-specific mtDNA deletions and microsatellite instability (MSI). We also performed mtDNA haplogrouping in 128 patients and 90 controls to identify its possible association with endometriosis risk. PRINCIPAL FINDINGS: We identified 51 somatic (novel: 31; reported: 20) and 583 germ-line mtDNA variations (novel: 53; reported: 530) in endometriosis patients. The A13603G, a novel missense mutation which leads to a substitution from serine to glycine at the codon 423 of ND5 gene showed 100% incidence in ectopic tissues. Interestingly, eutopic endometrium and peripheral leukocytes of all the patients showed heteroplasmy (A/G; 40-80%) at this locus, while their ectopic endometrium showed homoplasmic mutant allele (G/G). Superimposition of native and mutant structures of ND5 generated by homology modeling revealed no structural differences. Tumor-specific deletions and MSI were not observed in any of the ectopic tissues. Haplogrouping analysis showed a significant association between haplogroup M5 and endometriosis risk (P: 0.00069) after bonferroni correction. CONCLUSIONS: Our findings substantiate the rationale for exploring the mitochondrial genome as a biomarker for the diagnosis of endometriosis.
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Authors | Suresh Govatati, Nageswara Rao Tipirisetti, Shyam Perugu, Vijaya Lakshmi Kodati, Mamata Deenadayal, Vishnupriya Satti, Manjula Bhanoori, S Shivaji |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 7
Pg. e40668
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 22815783
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Mitochondrial
- Mitochondrial Proteins
- MT-ND5 protein, human
- Electron Transport Complex I
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Topics |
- Amino Acid Sequence
- Base Sequence
- Case-Control Studies
- Computational Biology
- DNA Mutational Analysis
- DNA, Mitochondrial
(genetics)
- Electron Transport Complex I
(chemistry, genetics)
- Endometriosis
(genetics, pathology)
- Female
- Gene Deletion
- Genetic Predisposition to Disease
- Genetic Variation
- Genome, Mitochondrial
(genetics)
- Germ-Line Mutation
(genetics)
- Haplotypes
(genetics)
- Humans
- India
- Microsatellite Instability
- Mitochondria
(genetics, metabolism)
- Mitochondrial Proteins
(chemistry, genetics)
- Molecular Sequence Data
- Mutation, Missense
- Neoplasm Staging
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