Variability of Mitochondrial DNA Heteroplasmy: Association with Asymptomatic Carotid Atherosclerosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. Ultrasonography of Carotid Arteries
2.3. MtDNA Heteroplasmy Measurements
- for mutations m.5178C>A, m.652delG, and m.652insG—60 °C;
- for mutations m.12315G>A, m.14459G>A, and m.1555A>G—50 °C;
- for mutations m.14846G>A, m.13513G>A, m.15059G>A, and m.3256C>T—55 °C.
2.4. Statistics
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mutation | Primers | Size of DNA Amplicons |
---|---|---|
m.12315G>A | F: bio-CTCATGCCCCCATGTCTAA (12230–12249) R: TTACTTTTATTTGGAGTTGCAC (12337–12317) | 108 bp |
m.652delG | F: TAGACGGGCTCACATCAC (621–638) R: bio-GGGGTATCTAATCCCAGTTTGGGT (1087–1064) | 467 bp |
m.14459G>A | F: CAGCTTCCTACACTATTAAAGT (14303–14334) R: bio-GTTTTTTTAATTTATTTAGGGGG (14511–14489) | 209 bp |
m.5178C>A | F: bio-GCAGTTGAGGTGGATTAAAC (4963–4982) R: GGAGTAGATTAGGCGTAGGTAG (5366–5345) | 383 bp |
m.13513G>A | F: CCTCACAGGTTTCTACTCCAAA (13491–13512) R: bio-AAGTCCTAGGAAAGTGACAGCGAGG (13825–13806) | 335 bp |
m.652insG | F: TAGACGGGCTCACATCAC (621–638) R: bio-GGGGTATCTAATCCCAGTTTGGGT (1087–1064) | 467 bp |
m.3256C>T | F: bio-AGGACAAGAGAAATAAGGCC (3129–3149) R: ACGTTGGGGCCTTTGCGTAG (3422–3403) | 294 bp |
m.15059G>A | F: bio-CATTATTCTCGCACGGACT (14671–14689) R: GCTATAGTTGCAAGCAGGAG (15120–15100) | 450 bp |
m.1555A>G | F:TAGGTCAAGGTGTAGCCCATGAGGTGGCAA (1326–1355) R: bio-GTAAGGTGGAGTGGGTTTGGG (1704–1684) | 379 bp |
m.14846G>A | F: bio-CATTATTCTCGCACGGACT (14671–14689) R: GCTATAGTTGCAAGCAGGAG (15120–15100) | 450 bp |
Mutation | Primer |
---|---|
m.12315G>A | TTTGGAGTTGCAC (12328–12316) |
m.652delG | CCCATAAACAAATA (639–651) |
m.14459G>A | GATACTCCTCAATAGCCA (14439–14456) |
m.5178C>A | ATTAAGGGTGTTAGTCATGT (5200–5181) |
m.13513G>A | AGGTTTCTACTCCAA (13497–13511) |
m.652insG | CCCATAAACAAATA (639–651) |
m.3256C>T | AAGAAGAGGAATTGA (3300–3286) |
m.15059G>A | TTTCTGAGTAGAGAAATGAT (15080–15061) |
m.1555A>G | ACGCATTTATATAGAGGA (1537–1554) |
m.14846G>A | GCGCCAAGGAGTGA (14861–14848) |
Characteristics | First Sample a | Second Sample b | Difference, p |
---|---|---|---|
Sex, male/female | 61/170 | 70/151 | 0.182 |
Age, years | 63.0 (5.9) | 61.6 (5.0) | 0.058 |
BMI, kg/m2 | 28.9 (4.9) | 28.7 (4.8) | 0.597 |
Diabetes, % | 5 | 6 | 0.782 |
Systolic BP, mm Hg | 130 (16) | 130 (15) | 0.900 |
Diastolic BP, mm Hg | 80 (9) | 81 (9) | 0.817 |
Smoking, % | 8 | 10 | 0.436 |
Carotid IMT, mm | 0.828 (0.115) | 0.694 (0.100) | <0.001 c |
Total cholesterol, mg/dL | 229.5 (40.1) | 234.2 (45.6) | 0.248 |
HDL, mg/dL | 49.1 (12.6) | 50.3 (16.4) | 0.387 |
LDL, mg/dL | 157.6 (34.6) | 160.6 (42.8) | 0.414 |
TG, mg/dL | 115.0 (60.7) | 119.3 (80.6) | 0.519 |
mtDNA Mutation | First Sample a | Second Sample b | Difference, p |
---|---|---|---|
m.5178C>A | 11.8 (9.6) | 6.8 (7.8) | <0.001 c |
m.1555A>G | 22.3 (13.1) | 23.0 (10.3) | 0.542 |
m.13513G>A | 22.7 (11.9) | 32.1 (16.2) | <0.001 c |
m.652delG | 23.8 (11.0) | 19.9 (10.2) | <0.001 c |
m.14846G>A | 16.4 (15.7) | 19.7 (16.6) | 0.030 d |
m.12315G>A | 35.5 (24.2) | 31.1 (21.1) | <0.043 d |
m.14459G>A | 5.1 (5.4) | 4.2 (4.7) | 0.055 |
m.652insG | 1.4 (9.8) | 3.9 (13.5) | 0.027 d |
m.3256C>T | 16.4 (16.5) | 11.6 (8.6) | 0.001 c |
m.15059G>A | 11.2 (14.3) | 9.8 (10.1) | 0.226 |
mtDNA Mutation | r, Pearson’s Correlation Coefficient | Significance, p |
---|---|---|
m.5178C>A | 0.274 | <0.001 ** |
m.1555A>G | −0.029 | 0.542 |
m.652delG | 0.184 | <0.001 ** |
m.12315G>A | 0.097 | 0.041 * |
m.14459G>A | 0.091 | 0.055 |
m.3256C>T | 0.180 | <0.001 ** |
m.15059G>A | 0.057 | 0.226 |
m.13513G>A | −0.316 | <0.001 ** |
m.652insG | −0.105 | 0.027 * |
m.14846G>A | −0.102 | 0.030 * |
Model | Minus Twice the Log Likelihood | Cox and Snell R2 | Nagelkerke R2 |
---|---|---|---|
1 | 147,273 | 0.358 | 0.481 * |
Model | Detected Cases | Predicted Cases | |||
---|---|---|---|---|---|
Association of Atherosclerotic Plaques with Total Burden of 10 Mutation | Percentage of Correct Predictions | ||||
0.00 | 1.00 | ||||
1 | Association of atherosclerotic plaques with total burden of 10 mutations | 0.00 | 18 | 7 | 24.6 |
1.00 | 11 | 37 | 50.6 | ||
Total percentage value | 75.3 * |
Analyzed Variables | |||||||
---|---|---|---|---|---|---|---|
Mutations | B | S.E. | Wald | df | Sig. | Exp (B) | |
Model 1 | m.1555A>G | −0.174 | 0.042 | 15.951 | 1 | 0.0001 ** | 0.840 |
m.3256C>T | 0.022 | 0.051 | 0.557 | 1 | 0.420 | 1.022 | |
m.14846G>A | −0.021 | 0.029 | 0.795 | 1 | 0.258 | 0.979 | |
m.5178C>A | 0.034 | 0.045 | 0.760 | 1 | 0.355 | 1.034 | |
m.652delG | 0.063 | 0.022 | 6.751 | 1 | 0.012 ** | 1.065 | |
m.12315G>A | 0.133 | 0.017 | 21.961 | 1 | 0.0001 ** | 1.42 | |
m.13513G>A | −0.051 | 0.019 | 6.871 | 1 | 0.006 ** | 0.950 | |
m.14459G>A | 0.031 | 0.015 | 2.862 | 1 | 0.043 ** | 1.031 | |
m.15059G>A | 0.061 | 0.021 | 7.766 | 1 | 0.0001 ** | 1.062 | |
m.652insG | 0.072 | 0.080 | 0.991 | 1 | 0.453 | 1.074 | |
Constant | −2.371 | 1.301 | 4.226 | 1 | 0.048 * | 0.093 |
Probability of Faultless Prognosis | ||||
---|---|---|---|---|
Area under the Curve | Standard Error | Asymptomatic Significance | Asymptomatic Confidence Interval 95% | |
Lower than 95% | Higher than 95% | |||
0.867 | 0.020 | 0.0015 | 0.771 | 0.910 |
OR | Risk of ASP in Carotid Arteries | Sensitivity | Specificity |
---|---|---|---|
4.5 (95% CI: 2.4–6.8) | 2.08 (95% CI: 1.51–3.53) | 0.749 | 0.858 |
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Sazonova, M.A.; Kirichenko, T.V.; Ryzhkova, A.I.; Sazonova, M.D.; Doroschuk, N.A.; Omelchenko, A.V.; Nikiforov, N.G.; Ragino, Y.I.; Postnov, A.Y. Variability of Mitochondrial DNA Heteroplasmy: Association with Asymptomatic Carotid Atherosclerosis. Biomedicines 2024, 12, 1868. https://doi.org/10.3390/biomedicines12081868
Sazonova MA, Kirichenko TV, Ryzhkova AI, Sazonova MD, Doroschuk NA, Omelchenko AV, Nikiforov NG, Ragino YI, Postnov AY. Variability of Mitochondrial DNA Heteroplasmy: Association with Asymptomatic Carotid Atherosclerosis. Biomedicines. 2024; 12(8):1868. https://doi.org/10.3390/biomedicines12081868
Chicago/Turabian StyleSazonova, Margarita A., Tatiana V. Kirichenko, Anastasia I. Ryzhkova, Marina D. Sazonova, Natalya A. Doroschuk, Andrey V. Omelchenko, Nikita G. Nikiforov, Yulia I. Ragino, and Anton Yu. Postnov. 2024. "Variability of Mitochondrial DNA Heteroplasmy: Association with Asymptomatic Carotid Atherosclerosis" Biomedicines 12, no. 8: 1868. https://doi.org/10.3390/biomedicines12081868