Department of Biology, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.
Department of Biology, Faculty of Science, Naresuan University, Phitsanulok, Thailand.
PLoS One. 2024 Jul 11;19(7):e0307036. doi: 10.1371/journal.pone.0307036. eCollection 2024.
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.
先前有几项研究报告指出，线粒体 (mt) DNA 的变异和单倍群与不同人群的各种疾病有关，包括心血管疾病，但这些研究尚未在泰国进行。在这里，我们对 82 名被诊断患有三种心血管疾病的患者（肥厚型心肌病 (HCM) (n = 26)、长 QT 综合征 (LQTS) (n = 7) 和 Brugada 综合征 (BrS) (n = 49)）的完整 mtDNA 基因组进行了测序，并将这些患者的 mtDNA 基因组与之前采访过的来自同一东北泰国地理区域的 750 名正常个体的线粒体基因组序列进行了比较。我们在 HCM、LQTS 和 BrS 患者中分别发现了 9、2 和 5 个新的突变，这些突变既不具有破坏性也不具有危害性。在 HCM 患者中，单倍群 R9c 与 HCM 显著相关（P = 0.0032；OR = 62.42；95%CI = 6.892-903.4），而单倍群 M12b 与 LQTS 显著相关（P = 0.0039；OR = 32.93；95%CI = 5.784-199.6）。在 BrS 患者中，没有发现任何单倍群与 BrS 显著相关。在 HCM 和 BrS 患者的 rRNA 基因中发现了显著更高密度的 mtDNA 变异（P < 0.001），而在 LQTS 或对照组患者中则没有。还预测了所有线粒体基因组中蛋白质编码或 tRNA 基因中检测到的 SNP 的影响。有趣的是，两个 BrS 患者的两个 tRNA 基因（MT-TA m.5618T>C 和 m.5631G>A 异质变体）和一个 HCM 患者的 MT-TQ m.4392C>T 新同质变体）中的三个 SNP 被预测会改变 tRNA 二级结构，可能导致 tRNA 功能异常。
