Interactions between diabetic and hypertensive drugs: a pharmacogenetics approach.

Diabetes is known to increase susceptibility to hypertension due to increase in inflammation, oxidative stress, and endothelial dysfunction, leading to vascular stiffness. The polytherapy might lead to several drug-drug interactions (DDIs), which cause certain life-threatening complications such as diabetic nephropathy and hypoglycaemia. So, in this review we focused on drug-drug interactions and impact of genetic factors on drug responses for better disease management. Drug-drug interactions (DDIs) may act either synergistically or antagonistically. For instance, a combination of metformin with angiotensin II receptor antagonist or angiotensin-converting enzyme inhibitors (ACEIs) synergistically improves glucose absorption, whereas the same hypertensive drug combination with sulphonylurea might cause severe hypoglycaemia sometimes. Thiazolidinediones (TDZs) can cause fluid retention and heart failure when taken alone, but a combination of angiotensin II receptor antagonist with TZDs prevents these side effects. Interindividual genetic variation affects the DDI response. We found two prominent genes, GLUT4 and PPAR-γ, which are common targets for most of the drug. So, all of these findings established a connection between drug-drug interaction and genetics, which might be used for effective disease management.

Genetic polymorphisms of IL6 gene -174G > C and -597G > A are associated with the risk of COVID-19 severity.

Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (-597G > A and -174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (-174G > C) and rs1800797 (-597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (-174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (-597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having 'C' allele of IL6 (-174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (-174G > C) and rs1800797 (-597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that 'C' allele of rs1800795 (-174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.

Technology for Improving Street Dog Welfare and Capturing Data in Digital Format during Street Dog Sterilisation Programmes.

Street dogs survive on food handouts provided by individuals, or the wider community yet typically receive limited to no veterinary care. They can also carry a variety of zoonotic diseases such as rabies, posing a significant risk to human and dog population health. Dog sterilisation is one of the most humane and effective methods available to control street dog populations. Dog sterilisation programmes, particularly those operating at a large-scale, often face a variety of challenges including limited resources, staffing, and less-than-ideal facilities. Recordkeeping is often a challenge as well, which can complicate the return of a sterilised dog to their location of capture. Street dogs are territorial, and the return of a dog to an incorrect location is fraught with various welfare issues, as well as an increased risk of postoperative complications, including death. Humane Society International developed a mobile phone-based application called 'HSIApps' drawing on years of field experience and data collection in street dog location recording, as well as clinical and postoperative treatment. HSIApps facilitates the return of dogs back to their exact captured location, which ensures dog welfare, and generates reports of a variety of useful data variables to maximise the efficacy and reliability of sterilisation programmes.

Genetic Variants and Drug Efficacy in Tuberculosis: A Step toward Personalized Therapy.

Tuberculosis (TB) continues to be a major infectious disease affecting individuals worldwide. Current TB treatment strategy recommends the standard short-course chemotherapy regimen containing first-line drug, i.e., isoniazid, rifampicin, pyrazinamide, and ethambutol to treat patients suffering from drug-susceptible TB. Although Mycobacterium tuberculosis , the causing agent, is susceptible to drugs, some patients do not respond to the treatment or treatment may result in serious adverse reactions. Many studies revealed that anti-TB drug-related toxicity is associated with genetic variations, and these variations may also influence attaining maximum drug concentration. Thus, inter-individual diversities play a characteristic role by influencing the genes involved in drug metabolism pathways. The development of pharmacogenomics could bring a revolution in the field of treatment, and the understanding of germline variants may give rise to optimized targeted treatments and refine the response to standard therapy. In this review, we briefly introduced the field of pharmacogenomics with the evolution in genetics and discussed the pharmacogenetic impact of genetic variations on genes involved in the activities, such as anti-TB drug transportation, metabolism, and gene regulation.

Determinants in Tailoring Antidiabetic Therapies: A Personalized Approach.

Diabetes has become a pandemic as the number of diabetic people continues to rise globally. Being a heterogeneous disease, it has different manifestations and associated complications in different individuals like diabetic nephropathy, neuropathy, retinopathy, and others. With the advent of science and technology, this era desperately requires increasing the pace of embracing precision medicine and tailoring of drug treatment based on the genetic composition of individuals. It has been previously established that response to antidiabetic drugs, like biguanides, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and others, depending on variations in their transporter genes, metabolizing genes, genes involved in their action, etc . Responsiveness of these drugs also relies on epigenetic factors, including histone modifications, miRNAs, and DNA methylation, as well as environmental factors and the lifestyle of an individual. For precision medicine to make its way into clinical procedures and come into execution, all these factors must be reckoned with. This review provides an insight into several factors oscillating around the idea of precision medicine in type-2 diabetes mellitus.

Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a global health issue and develops into a broad range of illnesses from asymptomatic to fatal respiratory diseases. SARS-CoV-2 infection is associated with oxidative stress that triggers cytokine production, inflammation, and other pathophysiological processes. Glutathione-S-transferase (GST) is an important enzyme that catalyzes the conjugation of glutathione (GSH) with electrophiles to protect the cell from oxidative damage and participates in the antioxidant defense mechanism in the lungs. Thus, in this study, we investigated the role of GSTM1 and GSTT1 gene polymorphism with COVID-19 susceptibility, as well as its outcome. The study included 269 RT-PCR confirmed COVID-19 patients with mild (n = 149) and severe (n = 120) conditions. All subjects were genotyped for GSTM1 and GSTT1 by multiplex polymerase chain reaction (mPCR) followed by statistical analysis. The frequency of GSTM1-/- , GSTT1-/- and GSTM1-/- /GSTT1-/- was higher in severe COVID-19 patients as compared to mild patients but we did not observe a significant association. In the Cox hazard model, death was significantly 2.28-fold higher in patients with the GSTT1-/- genotype (p = 0.047). In combination, patients having GSTM1+/+ and GSTT1-/- genotypes showed a poor survival rate (p = 0.02). Our results suggested that COVID-19 patients with the GSTT1-/- genotype showed higher mortality.

Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients.

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19. The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0). We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331-4.609). These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.