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Complete mitochondrial genomes of patients from Thailand with cardiovascular diseases
Wipada Woravatin1, Rattanasak Wongkomonched2, Wichittra Tassaneeyakul3
1Department of Biology, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.
Insights
Mitochondrial DNA variations and haplogroups are linked to cardiovascular diseases in Thailand. Haplogroup R9c is associated with Hypertrophic Cardiomyopathy, and M12b with Long Q-T Syndrome.
Area of Science:
- Genetics
- Cardiology
- Mitochondrial Biology
Background:
- Mitochondrial DNA (mtDNA) variations and haplogroups have been linked to various diseases globally.
- Previous studies on mtDNA and cardiovascular diseases (CVDs) have not been conducted in Thailand.
- This study investigates the role of mtDNA in specific CVDs within the Thai population.
Purpose of the Study:
- To identify novel mtDNA mutations associated with Hypertrophic Cardiomyopathy (HCM), Long Q-T Syndrome (LQTS), and Brugada Syndrome (BrS).
- To determine the association of specific mtDNA haplogroups with these cardiovascular diseases in Thailand.
- To analyze the impact of mtDNA variants on gene function in CVD patients.
Main Methods:
- Sequencing of complete mtDNA genomes from 82 patients with HCM, LQTS, and BrS.
- Comparison of patient mtDNA sequences with 750 published sequences from a healthy Thai control group.
- Bioinformatic analysis to predict the functional impact of identified single nucleotide polymorphisms (SNPs).
Main Results:
- Nine, two, and five novel, damaging mutations were identified in HCM, LQTS, and BrS patients, respectively.
- Haplogroup R9c showed a significant association with HCM (P = 0.0032), and haplogroup M12b with LQTS (P = 0.0039).
- A higher density of mtDNA variants in rRNA genes was observed in HCM and BrS patients; some tRNA gene variants potentially affect tRNA structure and function.
Conclusions:
- Specific mtDNA haplogroups (R9c and M12b) are significantly associated with HCM and LQTS in the Thai population.
- Novel mtDNA mutations and variants in rRNA and tRNA genes may contribute to the pathogenesis of these cardiovascular diseases.
- This research highlights the importance of studying mtDNA in the context of cardiovascular health in diverse ethnic groups, particularly in Thailand.
Abstract:
Several previous studies have reported that both variation and haplogroups of mitochondrial (mt) DNA were associated with various kinds of diseases, including cardiovascular diseases, in different populations, but such studies have not been carried out in Thailand. Here, we sequenced complete mtDNA genomes from 82 patients diagnosed with three types of cardiovascular disease, i.e., Hypertrophic Cardiomyopathy (HCM) (n = 26), Long Q-T Syndrome (LQTS) (n = 7) and Brugada Syndrome (BrS) (n = 49) and compared these with 750 previously published mitogenome sequences from interviewed normal individuals as a control group. Both patient and control groups are from the same geographic region of northeastern Thailand. We found 9, 2, and 5 novel mutations that were not both damaging and deleterious in HCM, LQTS, and BrS patients, respectively. Haplogroup R9c was significantly associated with HCM (P = 0.0032; OR = 62.42; 95%CI = 6.892-903.4) while haplogroup M12b was significantly associated with LQTS (P = 0.0039; OR = 32.93; 95% CI = 5.784-199.6). None of the haplogroups was found to be significantly associated with BrS. A significantly higher density of mtDNA variants in the rRNA genes was found in patients with HCM and BrS (P < 0.001) than in those with LQTS or the control group. Effects of detected SNPs in either protein coding or tRNA genes of all the mitogenome sequences were also predicted. Interestingly, three SNPs in two tRNA genes (MT-TA m.5618T>C and m.5631G>A heteroplasmic variants in two BrS patients and MT-TQ m.4392C>T novel homoplasmic variant in a HCM patient) were predicted to alter tRNA secondary structure, possibly leading to abnormal tRNA function.
