Crosstalk of Cyclin-dependent kinase inhibitor 1A (CDKN1A) gene polymorphism with p53 and CCND1 polymorphism in breast cancer.

OBJECTIVE: Mutations and polymorphisms in genes of cell- cycle and apoptosis regulatory pathway influence the breast cancer risk. Analysis of single low penetrance mutant alleles may not reflect the precise risk association when analyzed alone. PATIENTS AND METHODS: A total of 115 DNA samples extracted from breast cancer patients and an equal number of age and sex-matched normal controls were used for polymorphic analysis. Genotyping for p21 rs1801270 and CCND1 rs603965 was done by PCR-RFLP method while AFLP method was used for p53 rs1042522 single nucleotide polymorphism detection. Statistical methods included simple mean±SD and correlation coefficient to analyze the risk of association of p21, p53 and CCND1 SNPs and breast cancer. RESULTS: Individuals harboring SNPs in p21, p53 and CCND1 genes namely rs1801270, rs1042522 and rs603965, respectively were rendered increasingly susceptible to developing breast cancer when compared with normal controls. CONCLUSIONS: Our report emphasizes the need of combinational analysis of low-penetrance mutant alleles to assess accurately their association with breast cancer risk. Future case-control studies analyzing gene-environment interactions across different populations may confirm reported risk associations of studied polymorphisms with developing breast cancer.

Impact of COVID-19 on the cerebrovascular system and the prevention of RBC lysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) uses Angiotensin- converting enzyme 2 (ACE2) receptors to infect host cells which may lead to coronavirus disease (COVID-19). Given the presence of ACE2 receptors in the brain and the critical role of the renin-angiotensin system (RAS) in brain functions, special attention to brain microcirculation and neuronal inflammation is warranted during COVID-19 treatment. Neurological complications reported among COVID-19 patients range from mild dizziness, headache, hypogeusia, hyposmia to severe like encephalopathy, stroke, Guillain-Barre Syndrome (GBS), CNS demyelination, infarcts, microhemorrhages and nerve root enhancement. The pathophysiology of these complications is likely via direct viral infection of the CNS and PNS tissue or through indirect effects including post- viral autoimmune response, neurological consequences of sepsis, hyperpyrexia, hypoxia and hypercoagulability among critically ill COVID-19 patients. Further, decreased deformability of red blood cells (RBC) may be contributing to inflammatory conditions and hypoxia in COVID-19 patients. Haptoglobin, hemopexin, heme oxygenase-1 and acetaminophen may be used to maintain the integrity of the RBC membrane.