Mitochondrial DNA Haplogroups and Variants Predispose to Chagas Disease Cardiomyopathy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Tissue Collection
2.2. Heart Tissue and Blood DNA Isolation
2.3. Mitochondrial DNA Copy Number Quantification
2.4. Mitochondrial Haplogroup Determination
2.5. Variant Annotations
2.6. Statistical Analysis
3. Results
MtDNA Copy Number Is Reduced in Heart of Chagas Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Haplogroup Lineage | End stage Heart Tissue Samples (CCC) | Healthy Hearts of Organ Donors (Control) |
---|---|---|
African | 19 (73%) | 4 (67%) |
European | 4 (15%) | 0 (0%) |
Native American/Asian | 2 (8%) | 1 (17%) |
Eurasian | 1 (4%) | 1 (17%) |
Groups | p Value | Relative Risk |
---|---|---|
Healthy individuals versus Chagas patients | 0.01 | 0.76 |
Healthy individuals versus moderate Chagas cardiomyopathy patients | 0.06 | 0.85 |
Healthy individuals versus severe Chagas cardiomyopathy patients | 0.07 | 0.86 |
Pos | Ref | Alt | Csq | Gene Symbol | dbSNP ID | Uniprot Name | Uniprot ID | AA Pos | AA Ref | AA Alt | Described as Pathogenic in the following Databases. |
---|---|---|---|---|---|---|---|---|---|---|---|
3565 | A | C | RNA | MT-ND1 | NU1M | P03886 | 87 | T | P | PolyPhen2, SIFT, PROVEAN, CADD, PhDSNP, SP, COVEC_WMV, MtoolBox | |
3579 | A | C | RNA | MT-ND1 | NU1M | P03886 | 91 | M | I | CADD, PhDSNP, MutationTaster, SNPDryad, Condel | |
5262 | G | A | RNA | MT-ND2 | NU2M | P03891 | 265 | A | T | CADD, PANTHER, Condel, | |
6571 | C | T | RNA | MT-CO1 | COX1 | P00395 | 223 | A | V | PROVEAN, EFIN_SP, CADD, PhDSNP, MutationTaster, Condel, PolyPhen2 transf | |
6873 | C | T | RNA | MT-CO1 | COX1 | P00395 | 324 | L | F | PolyPhen2, SIFT, Mutatiossessor, EFIN_SP, EFIN_HD, CADD, PANTHER, PhDSNP, MutationTaster, COVEC_WMV, MtoolBox, Mutatiossessor transf | |
6899 | G | C | RNA | MT-CO1 | rs1556423194 | COX1 | P00395 | 332 | M | I | Condel, PolyPhen2 transf, SIFT transf |
6909 | G | T | RNA | MT-CO1 | COX1 | P00395 | 336 | A | S | SIFT, CADD, PhDSNP | |
6915 | G | A | RNA | MT-CO1 | rs1603220687 | COX1 | P00395 | 338 | V | M | Condel, PolyPhen2 transf, SIFT transf |
7008 | G | T | RNA | MT-CO1 | COX1 | P00395 | 369 | D | Y | PolyPhen2, SIFT, FatHmm, PROVEAN, Mutatiossessor, EFIN_SP, EFIN_HD, CADD, PANTHER, PhDSNP, SP, MutationTaster, SNPDryad, COVEC_WMV, MtoolBox, APOGEE, Mutatiossessor transf | |
7072 | T | C | RNA | MT-CO1 | rs1603220760 | COX1 | P00395 | 390 | M | T | PolyPhen2, SIFT, EFIN_HD, CADD, PhDSNP, SP, MutationTaster, COVEC_WMV, MtoolBox |
7868 | C | T | RNA | MT-CO2 | rs1556423357 | COX2 | P00403 | 95 | L | F | PROVEAN, CADD, PANTHER, PhDSNP, Condel, PolyPhen2 transf |
8021 | A | G | RNA | MT-CO2 | rs1603221261 | COX2 | P00403 | 146 | I | V | Condel, PolyPhen2 transf |
8401 | A | C | INT | MT-ATP8 | ATP8 | P03928 | 12 | M | I | Condel, SIFT transf | |
8405 | A | G | INT | MT-ATP8 | rs1603221462 | ATP8 | P03928 | 14 | T | A | Condel, PolyPhen2 transf |
8527 | A | G | RNA | MT-ATP6 | rs878853003 | ATP6 | P00846 | 1 | M | V | PolyPhen2, MtoolBox |
8558 | C | G | RNA | MT-ATP8 | ATP8 | P03928 | 65 | P | A | PolyPhen2, FatHmm, PROVEAN, CADD, SP, COVEC_WMV, MtoolBox | |
8558 | C | G | RNA | MT-ATP8 | ATP6 | P00846 | 11 | A | G | CADD, PANTHER, PhDSNP | |
8566 | A | G | RNA | MT-ATP6 | rs3020563 | ATP6 | P00846 | 14 | I | V | SP, Condel |
8568 | C | T | RNA | MT-ATP8 | rs1603221589 | ATP8 | P03928 | 68 | S | F | PolyPhen2, FatHmm, EFIN_HD, CADD, SP, MtoolBox |
8618 | T | C | RNA | MT-ATP6 | rs28358885 | ATP6 | P00846 | 31 | I | T | Condel |
8632 | T | C | RNA | MT-ATP6 | rs1603221654 | ATP6 | P00846 | 36 | Y | H | PANTHER, Condel, PolyPhen2 transf |
8677 | A | C | RNA | MT-ATP6 | ATP6 | P00846 | 51 | K | Q | Condel, PolyPhen2 transf | |
8714 | C | T | RNA | MT-ATP6 | rs1603221724 | ATP6 | P00846 | 63 | T | I | FatHmm, PANTHER, Condel |
8795 | A | C | RNA | MT-ATP6 | ATP6 | P00846 | 90 | H | P | PolyPhen2, SIFT, PROVEAN, CADD, PANTHER, PhDSNP, SP, SNPDryad, COVEC_WMV, MtoolBox | |
8854 | G | A | RNA | MT-ATP6 | rs386829055 | ATP6 | P00846 | 110 | A | T | SIFT, CADD, PANTHER, PhDSNP, Condel |
8860 | A | G | RNA | MT-ATP6 | rs2001031 | ATP6 | P00846 | 112 | T | A | PROVEAN, PhDSNP, SP, Condel, PolyPhen2 transf |
8870 | T | C | RNA | MT-ATP6 | rs1556423560 | ATP6 | P00846 | 115 | M | T | Condel, PolyPhen2 transf |
8875 | T | C | RNA | MT-ATP6 | rs201123510 | ATP6 | P00846 | 117 | F | L | Condel, PolyPhen2 transf |
9261 | A | C | RNA | MT-CO3 | COX3 | P00414 | 19 | T | P | PolyPhen2, PROVEAN, EFIN_SP, CADD, PhDSNP, SP, SNPDryad, MtoolBox | |
9325 | T | C | RNA | MT-CO3 | rs879000531 | COX3 | P00414 | 40 | M | T | Condel, PolyPhen2 transf |
9717 | C | G | RNA | MT-CO3 | COX3 | P00414 | 171 | L | V | Condel, PolyPhen2 transf | |
9861 | T | C | RNA | MT-CO3 | rs878853060 | COX3 | P00414 | 219 | F | L | Condel, PolyPhen2 transf, SIFT transf |
9877 | T | A | RNA | MT-CO3 | COX3 | P00414 | 224 | M | K | MutationTaster, Condel | |
9880 | T | A | RNA | MT-CO3 | COX3 | P00414 | 225 | F | Y | Condel, PolyPhen2 transf | |
9896 | A | C | RNA | MT-CO3 | COX3 | P00414 | 230 | K | N | Condel, PolyPhen2 transf | |
9924 | T | G | RNA | MT-CO3 | COX3 | P00414 | 240 | W | G | PolyPhen2, PROVEAN, Mutatiossessor, EFIN_HD, CADD, VEST, PhDSNP, SP, SNPDryad, COVEC_WMV, MtoolBox | |
10677 | G | A | RNA | MT-ND4L | rs1603222944 | NU4LM | P03901 | 70 | E | K | FatHmm, PROVEAN, Mutatiossessor, EFIN_SP, CADD, PANTHER, PhDSNP, SP, MutationTaster, SNPDryad, Condel, MtoolBox, Mutatiossessor transf |
10750 | A | G | RNA | MT-ND4L | rs372297272 | NU4LM | P03901 | 94 | N | S | PROVEAN, PhDSNP, MutationTaster, Condel |
10775 | G | A | RNA | MT-ND4 | rs879015842 | NU4M | P03905 | 6 | V | I | Condel, PolyPhen2 transf, SIFT transf |
10808 | C | T | RNA | MT-ND4 | rs2068723560 | NU4M | P03905 | 17 | L | F | CADD, Condel, MtoolBox |
10866 | T | C | RNA | MT-ND4 | rs1603222994 | NU4M | P03905 | 36 | I | T | Condel |
10972 | A | C | RNA | MT-ND4 | NU4M | P03905 | 71 | W | C | PolyPhen2, SIFT, FatHmm, PROVEAN, Mutatiossessor, EFIN_SP, EFIN_HD, CADD, PhDSNP, SP, SNPDryad, COVEC_WMV, MtoolBox, APOGEE, Mutatiossessor transf | |
11129 | A | G | RNA | MT-ND4 | rs1603223122 | NU4M | P03905 | 124 | T | A | Condel, SIFT transf |
11963 | G | A | RNA | MT-ND4 | rs201803948 | NU4M | P03905 | 402 | V | I | Condel, PolyPhen2 transf, SIFT transf |
12341 | C | A | RNA | MT-ND5 | NU5M | P03915 | 2 | T | N | Condel, PolyPhen2 transf | |
12346 | C | T | RNA | MT-ND5 | NU5M | P03915 | 4 | H | Y | Condel, PolyPhen2 transf, SIFT transf | |
12368 | C | T | RNA | MT-ND5 | NU5M | P03915 | 11 | T | I | FatHmm, PROVEAN, Condel, PolyPhen2 transf | |
12403 | C | T | RNA | MT-ND5 | NU5M | P03915 | 23 | L | F | Condel, PolyPhen2 transf | |
12802 | A | G | RNA | MT-ND5 | NU5M | P03915 | 156 | S | G | Condel | |
13034 | T | C | RNA | MT-ND5 | NU5M | P03915 | 233 | L | P | PolyPhen2, FatHmm, PROVEAN, Mutatiossessor, EFIN_SP, EFIN_HD, CADD, PANTHER, PhDSNP, SP, MutationTaster, SNPDryad, COVEC_WMV, MtoolBox, APOGEE, Mutatiossessor transf | |
13118 | T | A | RNA | MT-ND5 | NU5M | P03915 | 261 | I | N | PolyPhen2, FatHmm, PROVEAN, Mutatiossessor, EFIN_SP, CADD, PANTHER, PhDSNP, SP, SNPDryad, COVEC_WMV, MtoolBox, APOGEE, Mutatiossessor transf | |
13145 | G | A | RNA | MT-ND5 | NU5M | P03915 | 270 | S | N | Condel | |
13226 | A | C | RNA | MT-ND5 | NU5M | P03915 | 297 | D | A | PolyPhen2, FatHmm, PROVEAN, Mutatiossessor, EFIN_SP, CADD, PANTHER, PhDSNP, SP, MutationTaster, SNPDryad, COVEC_WMV, MtoolBox, APOGEE, Mutatiossessor transf | |
13303 | C | T | RNA | MT-ND5 | NU5M | P03915 | 323 | H | Y | PANTHER, PhDSNP, Condel, SIFT transf | |
13466 | G | A | RNA | MT-ND5 | NU5M | P03915 | 377 | S | N | FatHmm, PANTHER, Condel | |
13476 | A | T | RNA | MT-ND5 | NU5M | P03915 | 380 | L | F | PolyPhen2, FatHmm, PROVEAN, Mutatiossessor, EFIN_SP, EFIN_HD, CADD, PANTHER, PhDSNP, SP, SNPDryad, COVEC_WMV, MtoolBox, APOGEE, Mutatiossessor transf | |
13517 | A | T | RNA | MT-ND5 | NU5M | P03915 | 394 | H | L | PANTHER, Condel, PolyPhen2 transf | |
13600 | T | A | RNA | MT-ND5 | NU5M | P03915 | 422 | Y | N | PolyPhen2, FatHmmW, FatHmm, PROVEAN, Mutatiossessor, EFIN_SP, CADD, PANTHER, PhDSNP, SP, SNPDryad, COVEC_WMV, MtoolBox, APOGEE, DEOGEN2, Mutatiossessor transf | |
13614 | A | T | RNA | MT-ND5 | NU5M | P03915 | 426 | M | I | Condel | |
13618 | C | T | RNA | MT-ND5 | NU5M | P03915 | 428 | L | F | Condel, MtoolBox | |
13651 | A | G | RNA | MT-ND5 | rs1569484594 | NU5M | P03915 | 439 | T | A | CADD, Condel, MtoolBox |
13763 | C | A | RNA | MT-ND5 | NU5M | P03915 | 476 | S | Y | PolyPhen2, PROVEAN, CADD, PANTHER, SP, Condel, MtoolBox, SIFT transf | |
13804 | G | A | RNA | MT-ND5 | rs1603224360 | NU5M | P03915 | 490 | A | T | PolyPhen2, PROVEAN, CADD, PhDSNP, SP, SNPDryad, COVEC_WMV, MtoolBox |
13816 | A | C | RNA | MT-ND5 | NU5M | P03915 | 494 | T | P | PolyPhen2, FatHmm, PROVEAN, Mutatiossessor, CADD, PANTHER, PhDSNP, SP, SNPDryad, COVEC_WMV, MtoolBox, Mutatiossessor transf | |
13886 | T | C | RNA | MT-ND5 | rs28359182 | NU5M | P03915 | 517 | L | P | PhDSNP, Condel |
14170 | A | T | RNA | MT-ND6 | NU6M | P03923 | 168 | I | M | PolyPhen2, MtoolBox | |
14172 | T | G | RNA | MT-ND6 | NU6M | P03923 | 168 | I | L | PolyPhen2, CADD, MtoolBox | |
14280 | A | G | RNA | MT-ND6 | NU6M | P03923 | 132 | S | P | FatHmm, PhDSNP, Condel | |
14562 | C | T | RNA | MT-ND6 | NU6M | P03923 | 38 | V | I | Condel | |
14757 | T | C | RNA | MT-CYB | rs1603224859 | CYB | P00156 | 4 | M | T | Condel, PolyPhen2 transf |
14793 | A | G | RNA | MT-CYB | rs2853504 | CYB | P00156 | 16 | H | R | PhDSNP, SP, Condel, PolyPhen2 transf |
14798 | T | C | RNA | MT-CYB | rs28357681 | CYB | P00156 | 18 | F | L | Condel, PolyPhen2 transf |
14871 | T | C | RNA | MT-CYB | rs28660155 | CYB | P00156 | 42 | I | T | PROVEAN, PhDSNP, Condel, PolyPhen2 transf |
14873 | C | A | RNA | MT-CYB | CYB | P00156 | 43 | L | I | Condel | |
14881 | C | G | RNA | MT-CYB | CYB | P00156 | 45 | I | M | PolyPhen2, FatHmm, PANTHER, PhDSNP, SP, MtoolBox | |
15077 | G | A | RNA | MT-CYB | rs201943501 | CYB | P00156 | 111 | E | K | PolyPhen2, PROVEAN, CADD, PhDSNP, SNPDryad, MtoolBox |
15596 | G | A | RNA | MT-CYB | rs1603225369 | CYB | P00156 | 284 | V | I | Condel |
15617 | G | A | RNA | MT-CYB | rs1556424625 | CYB | P00156 | 291 | V | I | PolyPhen2, CADD, PhDSNP, SP, COVEC_WMV, MtoolBox |
15664 | C | A | RNA | MT-CYB | rs1603225414 | CYB | P00156 | 306 | I | M | CADD, Condel |
15699 | G | A | RNA | MT-CYB | CYB | P00156 | 318 | R | H | PolyPhen2, FatHmm, PROVEAN, Mutatiossessor, EFIN_HD, CADD, PANTHER, PhDSNP, SNPDryad, COVEC_WMV, MtoolBox, Mutatiossessor transf | |
15725 | C | T | RNA | MT-CYB | rs1603225438 | CYB | P00156 | 327 | L | F | PANTHER, Condel |
15734 | G | A | RNA | MT-CYB | rs386829259 | CYB | P00156 | 330 | A | T | PhDSNP, Condel |
15777 | G | A | RNA | MT-CYB | rs879182710 | CYB | P00156 | 344 | S | N | CADD, PhDSNP, Condel |
15812 | G | A | RNA | MT-CYB | rs200336777 | CYB | P00156 | 356 | V | M | EFIN_SP, MutationTaster, Condel |
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Gallardo, F.; Brochet, P.; Goudenège, D.; Nunes, J.P.S.; Andrieux, P.; Ianni, B.M.; Frade, A.F.; Mady, C.; Santos, R.H.B.; Kuramoto, A.; et al. Mitochondrial DNA Haplogroups and Variants Predispose to Chagas Disease Cardiomyopathy. Hearts 2023, 4, 97-117. https://doi.org/10.3390/hearts4040013
Gallardo F, Brochet P, Goudenège D, Nunes JPS, Andrieux P, Ianni BM, Frade AF, Mady C, Santos RHB, Kuramoto A, et al. Mitochondrial DNA Haplogroups and Variants Predispose to Chagas Disease Cardiomyopathy. Hearts. 2023; 4(4):97-117. https://doi.org/10.3390/hearts4040013
Chicago/Turabian StyleGallardo, Frédéric, Pauline Brochet, David Goudenège, João Paulo Silva Nunes, Pauline Andrieux, Barbara Maria Ianni, Amanda Farage Frade, Charles Mady, Ronaldo Honorato Barros Santos, Andreia Kuramoto, and et al. 2023. "Mitochondrial DNA Haplogroups and Variants Predispose to Chagas Disease Cardiomyopathy" Hearts 4, no. 4: 97-117. https://doi.org/10.3390/hearts4040013