Mutation Analysis of the Mitochondrial tRNA Genes in Iranian Coronary Atherosclerosis Patients
,
Abstract
Background: Atherosclerosis is a disease that affects large and medium size arteries in the body that underlies coronary heart disease. Several nucleotide changes in mitochondrial tRNA genes have been reported in various diseases. The purpose of the study was to identify hotspot mitochondrial tRNA mutations in atherosclerotic patients.
Methods: In this case-control study, the variations of ten mitochondrial tRNA genes (about 50%) were investigated in 70 patients from October 2013 and June 2015 suffered from atherosclerosis. The related mitochondrial area was amplified using PCR methid. The mutation analysis was performed by Single Strand Conformational Polymorphism (SSCP) and Restriction Fragment Length Polymorphism (RFLP). All the positive samples were sequenced.
Results: We found one novel heteroplasmic mutation (m.5725T>G) and three reported single nucleotide polymorphisms (SNPs) previously in other diseases including m.5568A>G, m.5711A>G and m.12308A>G.
Conclusion: These tRNA mutations can alter their steady state level and affect the structure of tRNA. The role of mitochondrial tRNA mutations in the pathogenesis of atherosclerosis could potentially be important for the understanding of mitochondrial dysfunction in coronary atherosclerotic plaque formation.
Fuster V, Kelly BB, Vedanthan R (2011). Promoting global cardiovascular health: moving forward. Circulation, 123(15):1671-8.
Moraes CT, Ciacci F, Bonilla E et al (1993). Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot? J Clin Invest, 92(6):2906-15.
Wick G, Knoflach M, Xu Q (2004). Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol, 22:361-403.
Nilsson J, Hansson GK (2008). Autoimmunity in atherosclerosis: a protective response losing control? J Intern Med, 263(5):464-78.
Grundtman C, Wick G (2011). The autoimmune concept of atherosclerosis. Curr Opin Lipidol, 22(5):327-34.
Tatarenkov A, Avise JC (2007). Rapid concerted evolution in animal mitochondrial DNA. Proc Biol Sci, 274(1619):1795-8.
Bandelt HJ, Kloss-Brandstatter A, Richards MB, Yao YG, Logan I (2014). The case for the continuing use of the revised Cambridge Reference Sequence (rCRS) and the standardization of notation in human mitochondrial DNA studies. J Hum Genet, 59(2):66-77.
Houshmand M, Panahi MS, Nafisi S, Soltanzadeh A, Alkandari FM (2006). Identification and sizing of GAA trinucleotide repeat expansion, investigation for D-loop variations and mitochondrial deletions in Iranian patients with Friedreich's ataxia. Mitochondrion, 6(2):82-8.
Heidari MM, Khatami M, Pourakrami J (2014). Novel Point Mutations in Frataxin Gene in Iranian Patients with Friedreich's Ataxia. Iran J Child Neurol, 8(1):32-6.
Montoya J, Ojala D, Attardi G (1981). Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs. Nature, 290(5806):465-70.
Pesole G, Gissi C, De Chirico A, Saccone C (1999). Nucleotide substitution rate of mammalian mitochondrial genomes. J Mol Evol, 48(4):427-34.
Holt IJ, Cooper JM, Morgan-Hughes JA, Harding AE (1988). Deletions of muscle mitochondrial DNA. Lancet, 1(8600):1462.
Salonen R, Nyyssonen K, Porkkala E et al (1995). Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation, 92(7):1758-64.
Heidari MM, Khatami M, Houshmand M, Mahmoudi E, Nafissi Sh (2011). Increased Prevalence 12308 A > G mutation in Mitochondrial tRNALeu (CUN) Gene Associated with earlier Age of Onset in Friedreich Ataxia. Iran J Child Neurol, 5(4):25-31.
Anderson S, Bankier AT, Barrell BG et al. (1981). Sequence and organization of the human mitochondrial genome. Nature, 290:457-65.
Kogelnik AM, Lott MT, Brown MD, Navathe SB, Wallace DC (1998). MITOMAP: a human mitochondrial genome database--1998 update. Nucleic Acids Res, 26(1):112-5.
Brown WM, George M, Jr, Wilson AC (1979). Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci U S A, 76(4):1967-71.
Sobenin IA, Sazonova MA, Postnov AY et al (2013). Changes of mitochondria in atherosclerosis: possible determinant in the pathogenesis of the disease. Atherosclerosis, 227(2):283-8.
Sobenin IA, Sazonova MA, Ivanova MM et al (2012). Mutation C3256T of mitochondrial genome in white blood cells: novel genetic marker of atherosclerosis and coronary heart disease. PLoS One, 7(10):e46573.
Murray CJ, Lopez AD (1997). Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet, 349(9061):p1269-76.
Chistiakov DA, Sobenin IA, Bobryshev YV, Orekhov AN (2012). Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes. World J Cardiol, 4(5):148-56.
Meulemans A, Seneca S, Lagae L et al (2006). A novel mitochondrial transfer RNA(Asn) mutation causing multiorgan failure. Arch Neurol, 63(8):1194-8.
Herrnstadt C, Elson JL, Fahy E et al (2002). Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups. Am J Hum Genet, 70(5):1152-71.
Shah AM, Tamang R, Moorjani P et al (2011). Indian Siddis: African descendants with Indian admixture. Am J Hum Genet, 89(1):154-61.
Jacobs HT, Hutchin TP, Kappi T et al (2005). Mitochondrial DNA mutations in patients with postlingual, nonsyndromic hearing impairment. Eur J Hum Genet, 13(1):26-33.
Chien MC, Huang WT, Wang PW et al (2012). Role of mitochondrial DNA variants and copy number in diabetic atherogenesis. Genet Mol Res, 11(3):3339-48.
van den Ouweland JM, Bruining GJ, Lindhout D et al (1992). Mutations in mitochondrial tRNA genes: non-linkage with syndromes of Wolfram and chronic progressive external ophthalmoplegia. Nucleic Acids Res, 20(4):679-82.
Covarrubias D, Bai RK, Wong LJ, Leal SM (2008). Mitochondrial DNA variant interactions modify breast cancer risk. J Hum Genet, 53(10):924-8.
Pulkes T, Sweeney MG, Hanna MG (2000). Increased risk of stroke in patients with the A12308G polymorphism in mitochondria. Lancet, 356(9247):2068-9.
| Files | ||
| Issue | Vol 46 No 10 (2017) | |
| Section | Original Article(s) | |
| Keywords | ||
| Atherosclerosis Mitochondrial tRNA Mutation PCR-SSCP | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
