First report on PARK-2 gene polymorphism and its relation to clinical pathological parameters and gene expression in
Gehan Abd-Elfatah Tawfeek1, Reham Ahmed Abdelaziz2
1Clinical Pathology Department, Faculty of Medicine, Menoufia University, Egypt.
Aim:
we investigated for first time Parkin (PARK2) gene polymorphism as a risk factor of Non-Hodgkin lymphoma (NHL) and the relation to the clinical pathological features and gene expression.
Materials And Methods:
The study involved 142 patients with NHL and 142 healthy control. Full histories, clinical examination, performance status, An Arbor staging, International prognostic index (IPI), patient survival and laboratory investigations such as LDH, β2microglobulin and Hepatitis C virus (HCV) RNA by qualitative real time PCR were performed for all subjects. PARK-2 gene polymorphism s (rs1801474, rs1801334) was determined by PCR-RFLP, PARK-2 mRNA was assessed by qRT-PCR.
Results:
According to GG as reference genotype, the genotypes (except GA) and A allele were significant risk factors for NHL (OR: 1.93-6.05; p = 0.004 - p < 0.001). A-G and A-A haplotypes increased the risk of NHL by 4.03 and 2.76 fold respectively (p < 0.001). It was found that AA and GA genotypes of both SNPs associated with poor performance status (p < 0.001). AA (and not GA) rs1801474 and AA &GA rs1801334 genotypes significantly associated with higher LDH (p < 0.001 & p < 0.001) and higher β2 microglobulin (p = 0.015 & p = 0.002) respectively, AA &GA genotypes of both SNPs have positive correlation with extra nodal sites and advanced staging (p < 0.001). AA genotype of both SNPs were associated with poor response to therapy and poor survival (p = 0.021 & p < 0.001). PARK-2 gene polymorphism has negative impact on PARK-2 gene expression.
Conclusion:
it is the first study to indicate that PARK-2 rs1801474 and rs1801334 SNPs carrying significant risk factors of NHL and it is correlated to some clinical pathological parameters may be due to down regulation of PARK-2 gene expression.
Abbreviations:
Non-Hodgkin lymphoma (NHL); diffuse large B cell lymphoma (DLBCL); follicular lymphoma (FL); and chronic lymphocytic leukemia (CLL); Over all survival (OS), progression free survival (PFS) and cancer specific survival (CSS); International prognostic index (IPI).
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