ABSTRACT Sudden cardiac events are the leading cause of death worldwide. Conventional risk stratification methods, which largely depend on clinical history, imaging, and electrocardiography, are usually inadequate for identifying high‐risk individuals, especially those without visible structural heart disease. Through genetic testing, personalized medicine has been revolutionized by enabling the identification of single‐gene variants, population‐specific polymorphisms, and polygenic risk factors that promote susceptibility to arrhythmia. Inherited channelopathies, such as long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia, as well as cardiomyopathies, are characterized by strong genotype–phenotype correlations, allowing more accurate prediction of arrhythmia risk. Single‐gene panels, whole‐exome sequencing (WES), whole‐genome sequencing (WGS), and polygenic risk scores (PRS) are not mutually exclusive; rather, they can be used together to enhance diagnostic yield and risk stratification. Screening of relatives of affected individuals enables the early identification of asymptomatic carriers. Moreover, the combination of clinical, imaging, and molecular data supports individualized risk assessment. The next steps emphasize the integration of multiomics, variant interpretation using artificial intelligence, and the creation of ancestry‐specific genetic repositories, which will facilitate predictive and preventive approaches to cardiology. This review describes current genetic testing approaches for sudden cardiac events, their use in personalized risk assessment, and the potential of personalized medicine to lower the risk of sudden cardiac death.

Gestational diabetes mellitus (GDM) is a common pregnancy complication with profound short- and long-term consequences for both mother and offspring. Beyond transient hyperglycemia, GDM represents a multifactorial metabolic condition shaped by the interplay of genetic predisposition, epigenetic regulation, and alterations in the maternal microbiome. Dysbiosis of the gut and reproductive tract microbiota contributes to inflammation, insulin resistance, and dyslipidemia during pregnancy, while microbial metabolites influence placental physiology and epigenetic remodeling of key metabolic and imprinted genes. These modifications, including changes in DNA methylation and non-coding RNA expression, link maternal hyperglycemia and microbial shifts to persistent alterations in gene expression that affect trophoblast activity, fetal growth trajectories, and long-term metabolic risk in offspring. Vertical transmission of maternal microbiota further imprints the neonatal microbiome, establishing an early-life foundation for reproductive and metabolic health. Although current diagnostic criteria and biomarkers remain inconsistent across populations, recent advances highlight the microbiome-epigenome axis as a promising source of predictive markers and therapeutic targets. Interventions such as probiotics, prebiotics, synbiotics, and dietary modulation show potential for improving maternal glycemic control, shaping placental function, and modulating fetal programming, although evidence for long-term efficacy is still emerging. Viewing GDM as both a metabolic stress test and a window of reproductive opportunity underscores the importance of early diagnosis and precision strategies. Integrating microbiome research and epigenetic insights into clinical practice offers new avenues to improve maternal outcomes, optimize fetal development, and reduce the intergenerational transmission of reproductive and metabolic disease risk.

INTRODUCTION:Coronary artery disease (CAD) is a multifactorial disorder influenced by both genetic and clinical risk factors. Lipid metabolism genes such as apolipoprotein B(APOB) (rs515135) and proprotein convertase subtilisin/kexin type 9 (PCSK9)(rs505151), have been associated with susceptibility to CAD. Study investigates the potential role of these genetic polymorphisms with risk of CAD in the Indian population. MATERIALS AND METHODS:A case-control study including 150 CAD cases and 150 controls. Angiographically proven Cases were recruited from the Cardiology Unit, Department of Medicine, Era's Lucknow Medical College. Genotyping was done using specific primers and restriction digestion; statistical analysis included t-tests, odds ratios, and haplotype analysis. RESULTS:CAD cases(mean age 49.93   ±   9.13 years) had higher serum cholesterol and VLDL but lower systolic and diastolic BP compared to controls (mean age 56.47   ±   9.39 years). The APOB G allele showed a significant protective effect against CAD (OR: 0.431,p = 0.001). CONCLUSION:The APOB G allele may serve as a protective factor against CAD, highlighting its potential role in genetic screening for lower disease risk. Further large-scale studies are required to confirm these findings.

This review explores how precision medicine is transforming the diagnosis, classification, and treatment of cardiomyopathies. It focuses on the integration of genetic profiling, biomarkers, and imaging to deliver more tailored and effective care. We review major cardiomyopathy subtypes: hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular, with a focus on genetic drivers, including mitochondrial mutations. Pediatric forms are discussed in the context of syndromic and non-syndromic differences. We highlight the clinical value of combining biomarkers (molecular and serological) with imaging modalities, such as echocardiography, for better risk stratification, especially in predicting sudden cardiac death. The utility of animal models in translating genetic findings into disease understanding is also emphasized. Finally, we touch on innovations like genome editing, gene therapies, and pharmacogenomics for personalized treatment. Precision medicine offers a promising future for cardiomyopathy care. By targeting the underlying causes and tailoring treatment to each patient's genetic and molecular profile, we can achieve more accurate diagnoses, better risk prediction, and improved outcomes, bringing us closer to truly individualized cardiovascular care.

COVID-19 manifestations range from asymptomatic to severe, and are influenced by host genetic factors. This study examined the association between vitamin D receptor (VDR) polymorphisms (TaqI and FokI) and transmembrane serine protease 2 (TMPRSS2) gene polymorphisms (rs12329760) and COVID-19 severity. 242 COVID-19 patients underwent genotyping using PCR-RFLP. Statistical analysis were conducted using SPSS v.21 and SHesis software, and validated by Sanger sequencing. The association of the VDR TaqI, FokI, and TMPRSS2 rs12329760 polymorphisms with COVID-19 severity was investigated. Computational analysis of TMPRSS2 was used to determine the pathogenicity and structural effects of these SNPs. For VDR TaqI, the ‘TC’ genotype showed higher prevalence in severe cases (50.5

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) unleashed a global pneumonia pandemic, causing significant harm to both physical and mental health. It emphasized the urgency for specialized therapies and protective measures. Approaches, including immunotherapy, antiviral drugs, and lifestyle improvements, like diet and exercise, have shown promise in controlling viral spread before widespread vaccination. However, COVID-19 vaccinations, while critical for reducing disease severity, have been associated with potential side effects, including transient cognitive impairment, rare renal disorders, physiologic anomalies, and dermatological reactions. The scientific community continues to rigorously study these issues to ensure the safety and efficacy of vaccination programs and to address the multifaceted impact of the pandemic.

BACKGROUND:Metformin-sulfonylurea combination is a widely prescribed as second-line therapy for type 2 diabetes mellitus (T2DM), yet patient responses vary due to individual genetic variation. These variations, particularly in AMP-activated protein kinase (AMPK) and its upstream regulator liver kinase B1 (LKB1), may contribute to differences in treatment response. This study investigated the association of PRKAA2(rs2746338) and LKB1(rs741765) polymorphisms with metformin-sulfonylurea response in T2DM patients. METHODS:We enrolled 193 T2DM patients on metformin-sulfonylurea therapy after obtaining written consent. Glycemic and lipid parameters were assessed at baseline and after 3 months. Genotyping was performed by PCR-RFLP and ARMS-PCR for PRKAA2(rs2746338) and LKB1(rs741765), respectively. Statistical analysis was conducted using SPSS v27. RESULTS:Genotype and allele distributions were not significantly different between responders and non-responders. Carriers of PRKAA2(rs2746338) AA and AG and LKB1(rs741765) CT genotypes showed greater FBG reduction (p = 0.028, p < 0.001, and p < 0.001 respectively). Additionally, PRKAA2(rs2746338) AG and LKB1(rs741765) CT genotypes showed significant improvements in PPG, HbA1c, triglycerides, and LDL (all p < 0.05). CONCLUSION:We conclude that PRKAA2(rs2746338) and LKB1(rs741765) variants were linked to favorable glycemic and lipid changes, suggesting reduced cardiovascular risk in T2DM. These variants may serve as pharmacogenetic markers for personalized therapy, warranting validation in larger studies.

Background Coronary artery disease (CAD) is a complex medical condition characterized by atherosclerotic plaque accumulation in coronary arteries, leading to narrowed blood vessels and impaired blood flow. Endothelial dysfunction, smooth muscle cell proliferation, and various risk factors contribute to CAD development. Matricellular proteins, including thrombospondins (THBS), play crucial roles in vascular processes and cardiac function. Methods A case–control study was conducted among 296 participants from Era's Lucknow Medical College and Hospital, India, to investigate genetic variations in THBS1 (N700S) and THBS2 (3′ UTR T → G) in relation to CAD. Genomic DNA was isolated, and PCR–RFLP was employed for genotyping. Clinical and biochemical parameters were assessed, and statistical analyses were performed using SPSS software. Results The study revealed that age, serum cholesterol, HDL, VLDL, and LDL were significantly associated with CAD in the Indian population. However, no statistically significant associations were found between triglyceride and serum creatinine levels, as well as the studied THBS1 and THBS2 genetic polymorphisms, and CAD. The analysis of genotypic and allelic frequencies did not indicate significant associations with CAD risk. Conclusions This study suggests that specific genetic variations in THBS1 and THBS2 may not be strongly linked to the development or risk of CAD in the studied Indian population. The associations observed between age, lipid profiles, and CAD highlight the multifactorial nature of CAD susceptibility. Further research with larger sample sizes and diverse populations is warranted to validate these findings and explore additional genetic factors contributing to CAD in specific populations.

Diabetes has become an epidemic in the developed world. Insulin resistance is a crucial element in diabetes development, occurring 10–20 years before the illness manifests itself. Insulin resistance has been linked to persistent low-grade inflammation. This chapter will go over several types of insulin resistance as well as the involvement of inflammatory biomarkers in insulin resistance. We found that numerous cytokines, including IL-10, IL-6, IL-1, TLR4, TNF-alpha, and NF-B, are found to play crucial roles in the development of insulin resistance. Getting active, controlling weight, taking medicine, managing stress, striving for appropriate sleep, adopting a balanced diet, cutting back on sugar and simple carbs, and consuming fiber-rich foods like whole grains, vegetables, beans, and lentils are important measures to reduce insulin resistance. These adjustments might reduce insulin resistance and enhance blood sugar regulation.

The severity of Coronavirus Disease 2019 (COVID-19) has been closely linked to an exacerbated proinflammatory response and cytokine storm. Interleukin-1 (IL-1), a pivotal proinflammatory cytokine, plays a crucial role in the development of acute respiratory distress syndrome (ARDS) and multiorgan dysfunction. Single nucleotide polymorphisms within the IL-1 gene have been shown to modulate IL-1 cytokine levels. This study aimed to investigate the association of IL-1 gene polymorphisms (IL-1 + 3953C > T, IL-1 beta -511 T > C, and IL-1Ra) with the severity of COVID-19. Genotyping of IL-1 gene polymorphisms (IL-1 + 3953C > T, IL-1 beta -511 T > C) were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while IL-1Ra genotyping was done by Random Amplification of Polymorphic DNA (RAPD). PCR-RFLP data were validated through Sanger sequencing (SeqStudio Genetic Analyzer). Data analysis was carried out by SPSS-v21 and SHesis (online version). The frequency of the T allele of the IL-1 + 3953C > T polymorphism was found to be higher in mild cases as compared to severe cases, demonstrating a significant protective effect against COVID-19 severity (P = 0.001). However, no significant associations were observed for IL-1 beta -511 T > C and IL-1Ra polymorphisms (P > 0.05). In haplotype analysis (between IL-1 + 3953C > T, and IL-1 beta -511 T > C gene polymorphisms), individual with CT haplotype showed a higher risk of severity (OR = 1.8, P = 0.001), while individuals with TT haplotype showed significant protection against severity (P = 0.001). Our findings suggest that the T allele of IL-1 beta + 3953C > T polymorphism may confer protective effect against the severity of COVID-19.

The intricate ecosystem of microorganisms residing within and on the human body, collectively known as the microbiome, significantly influences human health. Imbalances in this microbiome, referred to as dysbiosis, have been associated with various diseases, prompting the exploration of novel therapeutic approaches. Personalized medicine, Tailors treatments to individual patient characteristics, offers a promising avenue for addressing microbiome-related health issues. This review highlights recent developments in utilizing personalized medicine to target the microbiome, aiming to enhance health outcomes. Noteworthy strategies include fecal microbiota transplantation (FMT), where healthy donor microbes are transferred to patients, showing promise in treating conditions such as recurrent Clostridium difficile infection. Additionally, probiotics, which are live microorganisms similar to beneficial gut inhabitants, and prebiotics, non-digestible compounds promoting microbial growth, are emerging as tools to restore microbiome balance. The integration of these approaches, known as synbiotics, enhances microbial colonization and therapeutic effects. Advances in metagenomics and sequencing technologies provide the means to understand individual microbiome profiles, enabling tailored interventions. This paper aims to present the latest insights in leveraging personalized medicine to address microbiome-related health concerns, envisioning a future where microbiome-based therapies reshape disease management and promote human health.

The emergence of drug-resistant microorganisms has resulted in the reduced effectiveness of traditional antimicrobial therapies. The World Health Organization (WHO) has recognized antimicrobial resistance (AMR) in bacterial infections as a significant global health crisis. If effective measures are not established by 2050, it is projected that annual deaths from diseases caused by drug-resistant bacteria could reach up to 10 million people. Antimicrobial resistance (AMR) arises due to the transfer of bacteria and genes among humans, animals, and the environment. While there are inherent barriers that impede the unrestricted movement of bacteria and genes, the acquisition of new resistance factors from various species is a common occurrence. This phenomenon undermines our capacity to effectively prevent and treat bacterial infections, posing significant challenges. The core of the problem lies in the evolution of pathogens, which enables bacteria to rapidly adapt to the selective pressures imposed by the use of antimicrobials in medical and agricultural settings. This adaptation encourages the spread of resistance genes or alleles within bacterial populations. To combat these challenges, there is a growing focus on the development of precision antimicrobial treatments that target the key virulence characteristics of individual infections. This approach aims to tailor treatment to specific infections, considering their unique characteristics. In this article, we explore the benefits, advancements, and challenges associated with the development of precision antimicrobial medicines. The goal is to enhance our ability to effectively combat drug-resistant bacteria and mitigate the impact ofAMR on global health.

BACKGROUND: Hexachlorocyclohexane (HCH) is a widely distributed organochlorine pesticide and a well-known endocrine modulator. The population residing near the lindane manufacturing plant and its dumping sites in Lucknow, India are at high risk of HCH exposure.METHODS: A cross-sectional study was designed to investigate the reproductive toxicity of HCH in 57 HCH exposed and 57 unexposed men in relation to oxidative stress (malondialdehyde [MDA], glutathione [GSH]), genetic alteration in SRY and AZF gene, semen quality and infertility.RESULTS: The mean blood HCH level and MDA level were found significantly higher (P<0.01) in the exposed group as compared to the unexposed group. However, antioxidant glutathione (GSH) levels and semen quality were found significantly lower (P<0.01) in the exposed group as compared to the unexposed group. The prevalence of infertility was found to be significant (P<0.05) in the exposed group. Multiple correlation analyses showed the significant impact of HCH isomers on semen quality and oxidative stress parameters (GSH and MDA). The odds ratio for semen volume (OR=9.37, P=0.01), sperm motility (OR=28.75, P<0.01), and sperm count (OR=21.40, P<0.01), GSH (OR=0.97, P=0.01) MDA (OR=1.14, P<0.01) were found to be significant. We found three patients (5.3%) with Yq deletion in AZFa and AZFc regions in exposed men. In addition, the five subjects showed a mutation in the HMG box of the SRY gene.CONCLUSIONS: Our findings provide evidence that higher HCH exposure may cause oxidative damage to DNA in terms of AZF microdeletions and point mutation in the SRY gene, and poor semen quality, resulting in male infertility.

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.

Purpose To investigate the contradictory association of glaucoma with type 2 diabetes mellitus (T2DM) and its related factors that have been a springboard for a number of complications including glaucoma. Also, to examine the neuroprotective effects of antidiabetic medications. Recent Findings Recent studies suggest that T2DM may alleviate glaucoma risk or they may have common risk factors. Further, antidiabetic medications also exhibited neuroprotective properties in several studies. Summary Glaucoma is one of the complications significantly influenced by diabetes-induced metabolic changes in the body. Though the precise relationship between T2DM and glaucoma is still vague, various studies have aimed to investigate whether T2DM and its associated factors alleviate or aggravate glaucoma prognosis. These studies examined diverse aspects including anthropometric and demographic factors, lifestyle and dietary habits related to diabetes, in addition to genetics and antidiabetic medications, to establish their potential role in glaucoma risk, progression, and prevention. Despite numerous factors contributing to glaucoma progression, viz., loss of retinal ganglion cells, vision loss, etc., current antiglaucoma medications focus on reducing intraocular pressure. To bridge the existing gaps, other parameters must be addressed through interventions like lifestyle modifications, nutritional habits; or using antidiabetic drugs that are very likely protective against glaucoma incidence and progression. Additionally, genetic screening of high-risk individuals and glaucoma patients to assess drug response will greatly improve patient care. Thus, this review provides a comprehensive juxtaposition of both positive and negative implications of T2DM-associated factors in glaucoma to pave way for novel interventions and optimize patient outcomes in glaucoma management.

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.

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.

Background: Evidences suggest that single nucleotide polymorphisms (SNPs) can be considered as potential biomarkers for disease progression and therapeutic response in cervical cancer. The present study investigated the association of CYP1A1 T>C (rs4646903), CYP1A1 A>G (rs1048943), CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), XRCC1 G>A (rs25487), XRCC2 G>A (rs3218536) and XRCC3 C>T (rs861539) polymorphisms with treatment outcome of cisplatin based chemoradiation (CRT). Methods: Total 227 cervical cancer cases, treated with the same chemoradiotherapy regimen were selected for the study. Genotyping analysis was performed by PCR-restriction fragment length polymorphisms (PCR-RFLP). Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Association of all clinical data (responses, recurrence and survival of patients) and single nucleotide polymorphisms (SNPs) was analysed by using SPSS (version 21.0). Results: Patients with TA/AA genotype of CYP2E1 T>A polymorphism showed significantly poor response while those with GC/CC genotype of RAD51 G>C showed better response ( p = 0.008, p = 0.014 respectively). Death was significantly higher in patients with GG genotypes of RAD51 G>C and XRCC1 G>A ( p = 0.006, p = 0.002 respectively). Women with GC+CC genotype of RAD51 G>C and AG+GG of XRCC1 showed better survival and also reduced risk of death (HR = 0.489, p = 0.008; HR = 0.484, p = 0.003 respectively). Conclusion: Results suggested that CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), and XRCC1 G>A (rs25487) polymorphisms may be used as predictive markers for clinical outcomes in cervical cancer patients undergoing cisplatin based concomitant chemoradiotherapy.