Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics) - Volume 20, Issue 2, 2023

Biotin, a vitamin that is water-soluble, is part of the vitamin B complex and is required by all living things, including humans. Biotin-dependent carboxylases are a prosthetic group of enzymes, and biotin catalyzes essential processes in the production of fatty acids, the breakdown of amino acids, and gluconeogenesis in eukaryotic cells. The role of biotin as the prosthetic group of the four biotin-dependent carboxylases is well understood in higher animals. Based on the roles of these carboxylases in metabolism, it was discovered that biotin is required for cell survival, proliferation, and differentiation. Biotin appears to play a role in cell function and has a spermatogenic impact. Biotin has been found to have a direct impact on the transcription of important enzymes in glucose metabolism. Glucokinase and phosphoenolpyruvate carboxykinase are glycolytic enzymes that biotin controls (PEPCK). Biotin appears to be involved in gene control, which may explain some of its functions regarding fetal development and cellular biology. According to investigations using microarrays as well as other types of gene expression, biotin appears to affect the transcription of genes encoding cytokines and their receptors, glucose metabolism genes, and genes involved in cellular biotin homeostasis. A biotin shortage has a considerable effect on gene expression in numerous tissues and cells, according to a microarray study. Biotin supplementation affects the expression of several genes depending on the tissue, demonstrating that gene expression differences reflect tissue function. Biotin affects energy, lipid, and glucose metabolism, according to metabolite research, which has improved our understanding of the biotin metabolic pathway. Using microarray and transcriptome analysis, this research investigates the effect of biotin on gene expression.

Background: Several genetic alterations in cell growth regulatory genes, such as BRAF, are associated with colorectal cancer. Due to the introduction of biological agents designed to treat cancer, diagnostic tests using nucleic acids extracted from formalin-fixed and paraffin-embedded tissues are becoming more common.Objective: This study aimed to determine the incidence of BRAF mutations in colorectal cancer patients.Materials and Methods: 50 paraffin-embedded cancer specimens were obtained from Imam Reza Hospital of Birjand in Iran. PCR was used to amplify and sequence the BRAF gene exon 15, which was extracted from paraffin-embedded tissue using an improved technique.Results: 2/43 (4%) of patients with colorectal cancer exhibited the BEAF V600E mutation. Most of the mutations occurred in patients over 50 years of age.Conclusion: To understand how genetics and environment interact to influence the low incidence of BRAF mutations in the east of Iran, further research is needed to determine what is driving this low incidence of BRAF mutations and what factors contribute to it.

Background: Cathelicidin, a human host defense peptide, plays a salubrious role in innate host defense against human pathogens. Despite the extensive studies on the antimicrobial function of Cathelicidin, there is a lack of information on this peptide's deleterious single nucleotide polymorphisms (SNPs) that potentially alter the disease susceptibility and hence the current study.Objective: To predict Cathelicidin's structural and functional deleterious non-synonymous single nucleotide polymorphisms.Methods: The non-synonymous SNPs of Cathelicidin were investigated using computational prediction tools like SIFT, Polyphen, PROVEAN, MusiteDeep, I-Mutant, and STRING.Results: The present study predicted 23 potentially harmful nsSNP of Cathelicidin. Among these, 14 were highly conserved, 8 were average conserved, and 1 alone was variable. Phosphorylation was observed in serine and threonine residues using post-translational modification. Further mutation 3D predicted 11 clustered and 13 covered mutations in cathelicidin variants. The structural distribution of high-risk nsSNPs predicted 80 alpha helixes, 0 random coils, 19 extended strands, and 4 beta turns. Among 23 predicted deleterious SNPs, 9 nsSNPs alone showed mutation effect based on the HOPE structural and functional analysis. The direct functional interaction pattern of Cathelicidin with other proteins, FPR2, PRTN3, TLR9, IGF1R, and JUN, was observed.Conclusion: The identified deleterious nsSNPs could help understand the mutation effect of Cathelicidin in disease susceptibility and drug discovery.

Background: Several single nucleotide polymorphisms on methotrexate pathway have been implicated with hyperhomocysteinemia, susceptibility to autoimmune diseases and the therapy effectiveness of methotrexate.Objective: The present study estimates the ethnogeographic prevalence of rs1801133 (c.665C>T) in methylenetetrahydrofolate reductase and rs1051266 (c.80A>G) in solute carrier family 19 member 1, according to genomic ancestry analysis in Cuba healthy population.Methods: Genomic data was collected from a dense genome-wide genotyping array analysis of a large sample of individuals from all provinces of Cuba, with a final sample of 946 individuals for rs1801133 and 948 individuals for rs1051266.Results: For rs1801133, T allele and TT genotype were more prevalent in Mayabeque, the province with the highest European (p<0.0001) and the lowest African ancestry proportion (p<0.0001). Whereas, T allele and TT genotype frequency were low in Guantánamo (23.7% and 1.8%), the province with the highest African ancestry proportion (p<0.0001) and the lowest European ancestry proportion (p<0.0001). For rs1051266, the higher frequency of G allele was observed in Villa Clara, Las Tunas, Holguín and Granma and this group was associated with AG and GG genotypes (p=0.0045). This seems to be related to high Native American ancestry proportion in Las Tunas (p<0.0001), Holguín (p<0.0001) and Granma (p<0.0001); with the low African ancestry proportion in Villa Clara (p<0.0001) and with a Native American ancestry-enriched pattern observed for these provinces (p=0.0005).Conclusion: These results provide evidence that ancestry contribution impacts in the ethnogeographic prevalence of rs1801133 (c.665C>T) and rs1051266 (c.80A>G) polymorphisms in healthy Cuban individuals.

Background: Prostate cancer is one of the most commonly diagnosed malignancies in the developed world. Despite other risk factors like age, diet, environment and the pathogenesis of prostate cancer, recent advances in molecular genetics suggest that genetic inheritance plays an important role in prostate cancer.Objective: We attempted to analyze the association of SNPs rs4962416 and rs6465657 in the development of prostate cancer. A better understanding of the association of SNPs in prostate cancer susceptibility may improve risk prediction, improve precision mapping, and provide new insights into the underlying pathophysiology of prostate cancer. To date, no one has investigated these two SNPs in the Iranian populations, and according to the heterogeneity that exists, SNPs in communities should be examined separately.Methods: This case-control study includes 82 people with prostate adenocarcinoma as cases and 96 people with benign prostatic hyperplasia (BPH) as controls. Genotyping of each participant was done by TETRA ARMS-PCR method and for statistical analysis chi-squared, Fisher's exact logistic regression was used to find the SNPs associated with prostate cancer.Result: The frequency of the polymorphisms rs4962416 and rs6465657 in the prostate adenocarcinoma group was evaluated compared to the BPH control group (p-value < 0.05%) to choose the meaningful SNP. For rs4962416, we didn't find any meaningful association with prostatic cancer (p=0.402) but for rs6465657 there was a significant difference between genotype frequency (p=0.001).Conclusion: rs6465657 polymorphism which is associated with prostate cancer, can be chosen as a biomarker for this cancer and there should be more investigation on this SNP as these results need to be confirmed in a larger population.

This commentary explores the reasons why sex and gender differences must be included in medical education and the impact on healthcare outcomes for patients. Understanding sex and gender differences could be useful in making more accurate diagnoses and to develop more effective treatment plans. Sex and gender medicine take into consideration both the genetic basis and the effects of exposure to environmental and socio-economic factors.