Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
Department of Neurosciences, Brain Surgery Hospital, Rawalpindi, Pakistan.
PLoS One. 2019 Oct 14;14(10):e0223882. doi: 10.1371/journal.pone.0223882. eCollection 2019.
PARP-1 gene plays an essential part in base excision repair pathway and its functional variations result in several types of cancer. In this study we have explored the effect of genetic variations in PARP-1 gene in brain tumorigenesis. This case control study comprised of 500 brain tumor cases along with 500 healthy controls. Three polymorphisms of PARP-1 gene, rs1136410 (Val762Ala), rs1805404 (Asp81Asp) and rs1805414 (Ala284Ala) were analyzed using AS-PCR method followed by DNA sequencing. Joint effect model, haplotype analysis and linkage disequilibrium of these polymorphisms was assessed using Haploview 4.2. In rs1136410 (Val762Ala) heterozygous mutant genotype (CT) was observed notably lower (OR: 0.44., 95% CI: 0.33-0.57., p<0.0001) in brain tumor patients compared to controls and ~2 fold increased frequency of homozygous mutant genotype (CC) was observed in brain tumor patients versus controls (OR: 1.51., 95%CI: 1.16-1.96, p = 0.001). In rs1805414 (Ala284Ala), frequency of heterozygous mutant genotype (CT) was observed lower (OR: 0.77., 95% CI: 0.60-0.99., p = 0.05) in patients versus controls. In rs1805404 (Asp81Asp), heterozygous mutant genotyping (CT) was observed lower in brain tumor patients compared with the healthy controls (OR: 0.63., 95% CI: 0.48-0.83., p = 0.001). However, homozygous mutant genotype (TT) was observed increased in patients compared to controls (OR: 1.41., 95% CI:1.07-1.85., p = 0.01). We assessed the fact that in combination the PARP-1 gene SNPs, rs1136410 (Val762Ala), rs1805414 (Ala284Ala) and rs1805404 (Asp81Asp) may increase the brain pathogenesis at least in Pakistani population.
PARP-1 基因在碱基切除修复途径中起着至关重要的作用，其功能变异导致多种类型的癌症。本研究探讨了 PARP-1 基因遗传变异在脑肿瘤发生中的作用。这项病例对照研究包括 500 例脑肿瘤病例和 500 例健康对照。采用 AS-PCR 方法结合 DNA 测序，分析 PARP-1 基因的三个多态性位点：rs1136410（Val762Ala）、rs1805404（Asp81Asp）和 rs1805414（Ala284Ala）。采用 Haploview 4.2 评估这些多态性的联合效应模型、单体型分析和连锁不平衡。在 rs1136410（Val762Ala）中，杂合突变基因型（CT）在脑肿瘤患者中明显低于对照组（OR：0.44，95%CI：0.33-0.57，p<0.0001），而纯合突变基因型（CC）的频率在脑肿瘤患者中则高于对照组（OR：1.51，95%CI：1.16-1.96，p=0.001）。在 rs1805414（Ala284Ala）中，杂合突变基因型（CT）在脑肿瘤患者中的频率低于对照组（OR：0.77，95%CI：0.60-0.99，p=0.05）。在 rs1805404（Asp81Asp）中，与健康对照组相比，脑肿瘤患者的杂合突变基因型（CT）较低（OR：0.63，95%CI：0.48-0.83，p=0.001）。然而，与对照组相比，纯合突变基因型（TT）在患者中增加（OR：1.41，95%CI：1.07-1.85，p=0.01）。我们评估了以下事实，即至少在巴基斯坦人群中，PARP-1 基因 SNPs（rs1136410（Val762Ala）、rs1805414（Ala284Ala）和 rs1805404（Asp81Asp）的组合可能会增加脑发病机制。
