Current Pharmacogenomics and Personalized Medicine - Volume 22, Issue 1, 2025

Dental caries is a biofilm-mediated disease driven by dietary sugars that reduce pH and promote cariogenic microorganisms. Caries result from a complex interplay of behaviour, environmental, genetic, and physiological factors, with the immune response and bacterial activity contributing to enamel demineralization and cavity formation. Genetic factors, such as SNPs, also influence caries susceptibility, impacting enamel hardness and inflammatory responses.

This study aims to explore the association between the ALOX12 gene variant, rs9904779, and the susceptibility to dental caries.

Patients were recruited following ethical approval and informed consent. Saliva samples were collected and grouped by DMFT index, and genomic DNA was extracted. PCR analysis focused on ALOX12 gene polymorphism with the 223 bp product and RFLP. Statistical analysis was performed using Epi Info software, calculating genotype-risk associations and a significance threshold of p < 0.05. Chi-square testing assessed genotype and allele distributions across groups.

An SNP analysis of ALOX12 was conducted to assess the susceptibility of dental caries. In caries patients, CC genotype was most prevalent (42%), while CG was higher in controls (52%). Genotype distribution deviated from Hardy-Weinberg equilibrium in caries (p < 0.05) but not in controls (p > 0.05). The caries group had a higher prevalence of the C allele, while the CG heterozygote was more frequent in controls (OR = 0.64, p = 0.32).

This SNP analysis suggests that the ALOX12 gene variant rs9904779 may be a significant predictor for the development of dental caries, highlighting its potential as a genetic marker for susceptibility to the disease.

To examine whether novel lead hypertension molecules can be used in the personalized treatment of hypertension.

Hypertension is a modifiable condition that affects over 1 billion adults worldwide. Maintaining a healthy blood pressure is vital for overall health, especially given that hypertension is a primary risk factor for developing cardiovascular conditions. However, some individuals have resistant hypertension, which may be due to variations in genetic expression, making standard hypertension treatments ineffective.

The integration of genetic data into the personalized optimization of novel hypertension drugs is demonstrated.

This research created coding criteria for drug-gene recommendations based on the genomic profiles of ten pseudo-patients. The genomic data of these patients was created using chromosome and hypertension-implicated gene sequences from the NCBI National Library of Medicine database.

This study uses the proposed drug recommendation criteria to recommend novel hypertension lead molecules to each patient based on their gene expression profiles.

This study’s patient-centric drug prescription approach integrates patient gene expression data with drug-gene interaction data and recommends novel hypertension drugs most suitable for each patient. Variations in patient gene expression explain the diverse treatment responses inherent across hypertensive patients, thus necessitating a personalized approach to their drug prescription. Future studies can investigate the challenges of ethical, technological, and technical expertise that may affect the clinical implementation of personalized drug prescription recommendation systems.

Dental caries result from the demineralization of enamel or dentin caused by acids produced by cariogenic oral bacteria. The Glutathione S-transferase P1 (GSTP1) is a prominent member of the GST family, and it exhibits several genetic polymorphisms, with rs1695 being the most common variant.

Our study is to investigate the relationship between GSTP1 rs1695 polymorphism and the susceptibility to dental caries.

The study focused on understanding the relationship between GSTP1 rs1695 polymorphisms and susceptibility to dental caries in the Tamil population.

SNPs in the GSTP1 missense variant rs1695 (A/G) were analysed by PCR RFLP. The study group included 100 dental caries with (DMFT >5) and 100 healthy controls (DMFT=0). Further analysis of the impact of the GSTP1 wild-type gene with the rs1695 variant on mRNA's secondary structure was conducted using in silico prediction tools.

The results showed a significant frequency distribution of the heterozygous AG genotype (p<0.05). While the genotypic distribution of GSTP1 remained consistent with Hardy-Weinberg equilibrium (HWE) in the control group (p-value > 0.05), it deviated from HWE in the caries group. The free energy of the thermodynamic ensemble for the rs1695 variant was calculated to be -186.20 kcal/mol. This lower free energy, compared to the wild-type, indicates that the variant is more stable.

Our findings indicate that GSTP1 rs1695 variants could enhance susceptibility to dental caries by suggesting genetic load as a possible risk factor. However, additional functional research and larger studies are required to confirm these results.

Cancer is one of the serious health issues and the leading cause of mortality worldwide. Several studies have demonstrated that the overexpression of growth factors and receptors, the triggering of oncogenes, and the deactivation of tumor suppressor genes are the main causes of aggressive and resistant forms of cancer. The epidermal growth factor receptor (EGFR) is a receptor that medications target for cancer treatment.

The present study employs computational approaches to explore the anti-cancer activity of newly identified indole alkaloids from Zanthoxylum nitidum against EGFR kinase.

Computational techniques, including molecular docking, density functional theory (DFT), and in-silico pharmacokinetic studies, were employed to evaluate the ligand-target interactions. Additionally, drug-likeness was assessed using the Lipinski rule of five.

We evaluated their pharmacokinetics, binding interactions, and stability using molecular docking, drug-likeness prediction, absorption, distribution, metabolism, and excretion (ADMET) profiling, simulations study, and density functional theory (DFT) study. Nitidumalkaloid C showed remarkable binding affinity (-9.7 kcal/mol) to epidermal growth factor receptor tyrosine kinase, while that of standard drugs showed dacomitinib (-9.0 kcal/mol) and osimertinib (-7.9 kcal/mol). The molecular dynamics MD simulation study revealed stable interactions, with nitidumalkaloid C exhibiting the highest stability. These findings indicate indole alkaloids as potentially effective anticancer medicines, with nitidumalkaloid C demanding further modification for pharmaceutical development. This research informs nitidumalkaloid C as a potential indole alkaloid by providing insights into molecular characteristics and binding energies.

These parameters allow consideration of the most promising candidate, nitidumalkaloid C, for novel anticancer drug development to overcome gene mutations or resistance in EGFR-TK.