Accumulation of mtDNA Deletion (Delta mtDNA4977) showing Tissue-Specific and Age-Related Variation

Jeong, Hye Jin; Chung, Hyung Min; Cho, Sung Won; Kim, Hyun Ah; Lee, Kyung Sool; Kwon, Hwang; Choi, Dong Hee; Kwak, In Pyung; Yoon, Tae Ki; Lee, Sook Hwan

Abstract

OBJECTIVES
Controversial arguments exists on both the case for and against on the accumulation of mitochondrial DNA (mtDNA) deletion in association to tissue and age. The debate continues as to whether this mutation is a major contributor to the phenotypic expression of aging and common degenerative diseases or simply a clinical insignificant epiphenomenon. The objective of this study was to determine whether the accumulation of mtDNA deletion is correlated with age-related and tissue-specific variation.
MATERIALS AND METHODS
One hundred and fifty-seven tissues from blood, ovary, uterine muscle, and abdominal muscle were obtained from patients ranging in age from 31~60 years. After reviewing the clinical reports, patients with mitochondrial disorder were excluded from this study. The tissues were obtained at gynecological surgeries with the consent of the patient. Total DNA isolated from blood, ovary, uterine muscle, and abdominal muscle was amplified by two rounds of PCR using two pairs of primers corresponding to positions 8225-8247 (sense), 13551-13574 (antisense) for the area around deleted mtDNA and 8421-8440 (sense), 13520-13501 (antisense) for nested PCR product. A statistical analysis was performed by c2-test.
RESULTS
About 0% of blood, 94.8% of ovary, 71.4% of uterine muscle, and 86.1% abdominal muscle harbored mtDNA deletion. When we examined the proportion of deleted mtDNA according to age deletion rate was 90% of ovary, 63.6% of uterine muscle, 77.7% of abdominal muscle in thirties and 100% of all tissue in fifties.
CONCLUSION
The findings of this study suggest that the mtDNA deletion is varied in tissue-specific pattern and increases with aging.