Association of PARP1 SNP (rs1136410) with Brain Tumor Risk: Insights from Khyber Pakhtunkhwa

Brain tumors are among the most complex and life-threatening malignancies, with limited understanding of their genetic etiology. Poly (ADP-ribose) polymerase 1 (PARP1) plays a critical role in DNA repair. The single nucleotide polymorphism (SNP) rs1136410 (A>G) in PARP1, which results in a Val762Ala substitution, has been suggested to alter PARP1 enzymatic activity and potentially influence tumor development. However, its association with brain tumors remains underexplored particularly in the population of Khyber Pakhtunkhwa (KP), Pakistan.

In this study, we enrolled 200 patients with brain tumors, along with an additional 200 individuals as controls. DNA was extracted using the phenol-chloroform method, followed by genotyping through the Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Statistical analysis was conducted using GraphPad Prism.

The genotypic distribution of rs1136410 in brain tumor patients and healthy individuals indicates that this SNP is significantly associated with brain tumors (Chi-square = 13.24, df = 2, p = 0.0013). The AA genotype was associated with a 77% increased risk of overall brain tumors (OR = 1.77, p = 0.0065), an 88% increased risk of glioma (OR = 1.88, p = 0.0159), and a 2.9-fold increased risk of meningioma (OR = 2.91, p = 0.0073). In contrast, the GG genotype was associated with a 63% decreased risk of overall brain tumors (OR = 0.37, p = 0.0011), an 84% decreased risk of glioma (OR = 0.26, p = 0.0019), and an 80% decreased risk of meningioma (OR = 0.21, p = 0.0217). Similarly, the A allele was associated with an increased risk of brain tumors (OR = 1.88, p = 0.0065), whereas the G allele was associated with a decreased risk (OR = 0.53, p = 0.0001).

In conclusion, this study demonstrates that rs1136410 is significantly associated with brain tumor risk particularly with the glioma and meningioma subtypes underscoring the role of PARP1 in brain tumor genetics and its potential as a therapeutic target.