Fazal Ul Haq Maria, Hussain Muhammad Zahid, Haris Muhammad Shahbaz, Kayani Mahmood Akhtar, Mahjabeen Ishrat
Cancer Genetics and Epigenetics Research Group, Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
Department of Rheumatology, Military hospital, Rawalpindi, Pakistan.
Future Oncol. 2024 Dec;20(40):3421-3432. doi: 10.1080/14796694.2024.2429948. Epub 2024 Nov 19.
Previous studies on brain tumors have been performed on the nuclear genome, but limited studies have been reported on the mitochondrial genome. The mitochondrial sirtuin (SIRT3/SIRT4/SIRT5) has been mutated in different cancers. Limited studies have been performed on brain tumors. Isocitrate dehydrogenase (IDH) is an important marker, and polymorphism in the IDH gene has been reported to differentiate the brain tumor subtypes.
The present study was designed to screen mitochondrial sirtuins and IDH polymorphisms in brain tumor patients.
One thousand blood samples were collected (500 brain tumor patients and 500 controls). Two SNPs for each gene SIRT3 (rs12226697, rs570591), SIRT4 (rs184496260, 1925909), SIRT5 (rs2841522, rs2841523), and one SNP for IDH (rs11554137) was screened using Tetra-ARMS PCR.
Logistic regression showed that the mutant genotype of selected SNPs was associated with increased disease incidence compared to wild type. Haplotype analysis and linkage disequilibrium (LD) showed a strong LD in brain tumor patients. Kaplan-Meier analysis showed that mutant allele frequency was found to be associated with a significant decrease in the survival of brain tumor patients.
The present study showed that the mutant allele of selected mitochondrial sirtuins' SNP was associated with increased brain tumor risk.
先前关于脑肿瘤的研究是针对核基因组进行的，但关于线粒体基因组的报道较少。线粒体沉默调节蛋白（SIRT3/SIRT4/SIRT5）在不同癌症中发生了突变。针对脑肿瘤的相关研究较少。异柠檬酸脱氢酶（IDH）是一个重要标志物，据报道IDH基因的多态性可用于区分脑肿瘤亚型。
本研究旨在筛查脑肿瘤患者中线粒体沉默调节蛋白和IDH的多态性。
收集了1000份血样（500例脑肿瘤患者和500例对照）。使用四引物扩增受阻突变系统聚合酶链反应（Tetra-ARMS PCR）筛查每个基因SIRT3（rs12226697，rs570591）、SIRT4（rs184496260，1925909）、SIRT5（rs2841522，rs2841523）的两个单核苷酸多态性（SNP）以及IDH的一个SNP（rs11554137）。
逻辑回归显示，与野生型相比，所选SNP的突变基因型与疾病发病率增加相关。单倍型分析和连锁不平衡（LD）显示脑肿瘤患者中存在强连锁不平衡。Kaplan-Meier分析表明，突变等位基因频率与脑肿瘤患者生存率显著降低相关。
本研究表明，所选线粒体沉默调节蛋白SNP的突变等位基因与脑肿瘤风险增加相关。
