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. 2008 Aug 6;100(15):1104-12.
doi: 10.1093/jnci/djn213. Epub 2008 Jul 29.

Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma

Jinliang Xing  1 , Meng Chen, Christopher G Wood, Jie Lin, Margaret R Spitz, Jianzhong Ma, Christopher I Amos, Peter G Shields, Neal L Benowitz, Jian Gu, Mariza de Andrade, Gary E Swan, Xifeng Wu
Affiliations

Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma

Jinliang Xing et al. J Natl Cancer Inst. .

Abstract

Background: The extent to which mitochondrial DNA (mtDNA) content (also termed mtDNA copy number) in normal human cells is influenced by genetic factors has yet to be established. In addition, whether inherited variation of mtDNA content in normal cells contributes to cancer susceptibility remains unclear. Renal cell carcinoma accounts for 85% of all renal cancers. No studies have investigated the association between mtDNA content and the risk of renal cell carcinoma.

Methods: We first used a classic twin study design to estimate the genetic contribution to the determination of mtDNA content. mtDNA content was measured by quantitative real-time polymerase chain reaction in peripheral blood lymphocytes from 250 monozygotic twins, 92 dizygotic twins, and 33 siblings (ie, individual siblings of a pair of twins). We used biometric genetic modeling to estimate heritability of mtDNA content. We then used a case-control study with 260 case patients with renal cell carcinoma and 281 matched control subjects and multivariable logistic regression analysis to examine the association between mtDNA content in peripheral blood lymphocytes and the risk of renal cell carcinoma. All statistical tests were two-sided.

Results: The heritability (ie, proportion of phenotypic variation in a population that is attributable to genetic variation among individuals) of mtDNA content was 65% (95% confidence interval [CI] = 50% to 72%; P < .001). Case patients with renal cell carcinoma had a statistically significantly lower mtDNA content (1.18 copies) than control subjects (1.29 copies) (difference = 0.11, 95% CI = 0.03 to 0.17; P = .006). Low mtDNA content (ie, less than the median in control subjects) was associated with a statistically significantly increased risk of renal cell carcinoma, compared with high content (odds ratio = 1.53, 95% CI = 1.07 to 2.19). In a trend analysis, a statistically significant dose-response relationship was detected between lower mtDNA content and increasing risk of renal cell carcinoma (P for trend <.001).

Conclusions: mtDNA content appears to have high heritability. Low mtDNA content appears to be associated with increased risk of renal cell carcinoma.

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Figures

Figure 1
Figure 1
Intraclass correlation of mitochondrial DNA (mtDNA) content. A) Monozygotic twins. B) Dizygote pairs (pooled dizygotic twin pairs and monozygotic twin–sibling pairs). The first person within the dizygote pairs is defined as dizygotic person 1 and the second person within the pair is defined as dizygotic person 2. The straight lines in the scatter plots are the 45° line. All statistical tests were two-sided. The x- and y-axes represent mtDNA content for individuals 1 and 2, in both panels.
See this image and copyright information in PMC

References

    1. Fernandez-Silva P, Enriquez JA, Montoya J. Replication and transcription of mammalian mitochondrial DNA. Exp Physiol. 2003;88(1):41–56. - PubMed
    1. Gahan ME, Miller F, Lewin SR, et al. Quantification of mitochondrial DNA in peripheral blood mononuclear cells and subcutaneous fat using real-time polymerase chain reaction. J Clin Virol. 2001;22(3):241–247. - PubMed
    1. Diez-Sanchez C, Ruiz-Pesini E, Lapena AC, et al. Mitochondrial DNA content of human spermatozoa. Biol Reprod. 2003;68(1):180–185. - PubMed
    1. Barthelemy C, Ogier de Baulny H, Diaz J, et al. Late-onset mitochondrial DNA depletion: DNA copy number, multiple deletions, and compensation. Ann Neurol. 2001;49(5):607–617. - PubMed
    1. Cavelier L, Jazin EE, Eriksson I, et al. Decreased cytochrome-c oxidase activity and lack of age-related accumulation of mitochondrial DNA deletions in the brains of schizophrenics. Genomics. 1995;29(1):217–224. - PubMed

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