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Modulation of brain tumor risk by genetic SNPs in PARP1gene: Hospital based case control study


Autoři: Asad ullah Khan aff001;  Ishrat Mahjabeen aff001;  Muhammad Arif Malik aff002;  Muhammad Zahid Hussain aff003;  Sarfraz Khan aff004;  Mahmood Akhtar Kayani aff001
Působiště autorů: Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan aff001;  Department of Neurosciences, Brain Surgery Hospital, Rawalpindi, Pakistan aff002;  Department of Medicine, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan aff003;  Department of Physiotherapy, Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan aff004
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0223882

Souhrn

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.

Klíčová slova:

Haplotypes – Alleles – Polymerase chain reaction – Carcinogenesis – Variant genotypes – Linkage disequilibrium – Glioma – Meningioma


Zdroje

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2019 Číslo 10
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