Computational identification and analysis of deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in the human gene: a structural and functional impact.

Cytochrome P450 oxidoreductase (POR) protein is essential for steroidogenesis, and gene mutations are frequently associated with P450 Oxidoreductase Deficiency (PORD), a disorder of hormone production. To our knowledge, no previous attempt has been made to identify and analyze the deleterious/pathogenic non-synonymous single nucleotide polymorphisms (nsSNPs) in the human POR gene through an extensive computational approach. Computational algorithms and tools were employed to identify, characterize, and validate the pathogenic SNPs associated with certain diseases.

Influence of CYP2C9 Polymorphisms on Plasma Concentration of Warfarin and 7-Hydroxy Warfarin in South Indian Patients.

Background: Warfarin is primarily metabolized by cytochrome P450 2C9 (CYP2C9) enzyme, which is encoded by the CYP2C9 gene. CYP2C9*2 and CYP2C9*3 variants significantly influence warfarin metabolism and subsequently the required dose of warfarin.

Objectives: The current retrospective study was aimed to determine the influence of CYP2C9 variants on warfarin metabolic ratio (MR, warfarin/7-hydroxy warfarin) and warfarin maintenance therapy in 210 patients (mean age 44.

Polymorphisms of T- cell leukemia 1A gene loci are not related to the development of adjuvant letrozole-induced adverse events in breast cancer.

Letrozole, an aromatase inhibitor (AI), is the first-line adjuvant drug for treating hormone receptor-positive (HR+) breast cancer in postmenopausal women. However, harmful adverse events (AEs) and significant differences in drug response among individuals remain a significant problem in clinical application. Current evidence suggests that the observed individual variation in the treatment outcomes of AI is conferred by genetic variants.

Prothrombotic Factors Have Significant Association with Arterial and Venous Strokes in Indian Tamilians.

Background: Prothrombotic factors have been correlated with vascular events in young patients, with recurrent strokes, and with venous thromboembolisms. However, their prevalence in adult strokes, in healthy populations, and in specific ethnic groups is not well defined. We investigated the association of prothrombotic factors with strokes in a South Indian Tamil population.

Insight into the structural and functional analysis of the impact of missense mutation on cytochrome P450 oxidoreductase.

Cytochrome P450 oxidoreductase (POR) is a steroidogenic and drug-metabolizing enzyme. It helps in the NADPH dependent transfer of electrons to cytochrome P450 (CYP) enzymes for their biological activity. In this study, we employed integrative computational approaches to decipher the impact of proline to leucine missense mutation at position 384 (P384L) in the connecting/hinge domain region which is essential for the catalytic activity of POR.

Association of CYP19A1 gene variations with adjuvant letrozole-induced adverse events in South Indian postmenopausal breast cancer cohort expressing hormone-receptor positivity.

Purpose: Musculoskeletal adverse events (MS-AEs) and vasomotor symptoms (VMSs) are the major side-effects of newer generation non-steroidal aromatase inhibitor (AI), letrozole. Single-nucleotide polymorphisms (SNPs) in CYP19A1 gene coding for the enzyme aromatase are related to AI treatment-associated adverse drug reactions. Therefore, we aimed to determine whether SNPs in the CYP19A1 gene are associated with adjuvant letrozole-induced 'specific' AEs in postmenopausal hormone receptor-positive (HR+) breast cancer patients.

Effects of genetic polymorphisms in Vitamin D metabolic pathway on Vitamin D level and asthma control in South Indian patients with bronchial asthma.

Objectives: The study was designed to evaluate the single-nucleotide polymorphisms (SNPs) of genes involved in Vitamin D actions (rs2228570) and metabolic pathways (rs2248137 and rs10766197) and their associations with serum 25-hydroxy Vitamin D (25(OH)D) level and asthma control in South Indian patients with bronchial asthma.

Materials And Methods: One hundred and two patients of South Indian origin with bronchial asthma either naive to inhaled corticosteroids (ICSs) or not receiving ICS for ≥1 month were included and were treated with ICS (beclomethasone 200 μg twice daily) for 8 weeks. One hundred and one unrelated healthy South Indians were used as controls.

Ceftriaxone concentration at the surgical site following systemic and isolated upper limb injection.

Background And Aims: This study was conducted to find out the equipotent dose of isolated upper limb injection of ceftriaxone in the upper limb (IUL) surgeries under tourniquet that would attain a peak bone marrow concentration (Cmax) similar to systemic (ST) 1 g injection.

Material And Methods: Patients were allocated into two groups - ST and IUL. ST group ( = 5) received 1 g of ceftriaxone 20 min before tourniquet inflation, and IUL group received calculated dose ( = 5 in each dosage, i.

Drug information center as referral service in a South Indian tertiary care hospital.

Objective: The objective of this study is to assess the various aspects of drug information services (DISs) provided in the DI center of a tertiary care hospital.

Materials And Methods: DI queries received from various departments from April 2013 to May 2017 were included in the study. Various aspects such as year- and department-wise distribution, reason for sending the queries, mode of receipt and reply, time taken for reply, number of visit for bedside examination of patients, and number of references given per query were analyzed.

Vascular endothelial growth factor (VEGF) gene polymorphisms (rs699947, rs833061, and rs2010963) and psoriatic risk in South Indian Tamils.

Background: Psoriasis is a chronic inflammatory disease of the skin. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is involved in the pathogenesis of psoriasis. Being highly polymorphic, several SNPs of VEGF have been reported to be associated with increased risk of psoriasis.

The Impact of the Educational Intervention on Knowledge, Attitude, and Practice of Pharmacovigilance toward Adverse Drug Reactions Reporting among Health-care Professionals in a Tertiary Care Hospital in South India.

Background: Knowledge, attitude, practice (KAP)-based educational intervention is an important tool to reduce underreporting of adverse drug reactions (ADRs). Hence, this study aimed to assess the KAP of doctors and nurses working in medicine and allied departments of Jawaharlal Institute of Postgraduate Medical Education and Research on spontaneous reporting of ADRs, following an educational intervention. The study also compared the quantity of ADRs reported before and after 1 year of introducing the educational intervention.

Clinical Utility of Fractional exhaled Nitric Oxide (FeNO) as a Biomarker to Predict Severity of Disease and Response to Inhaled Corticosteroid (ICS) in Asthma Patients.

Introduction: Bronchial asthma is a common chronic inflammatory airway disease diagnosed and is based on symptomatic history and Pulmonary Function Tests (PFT). Fractional exhaled Nitric Oxide (FeNO) is exclusively a non-invasive biomarker of on-going eosinophilic airway inflammation which remains unpredictable only with PFTs. FeNO measurement is recommended in predicting asthma severity and Inhaled Corticosteroid (ICS) response but further research is required to understand its clinical utility and agreement with current recommendations in a specific population.

Association of C-Reactive Protein (rs1205) Gene Polymorphism with Susceptibility to Psoriasis in South Indian Tamils.

Introduction: Psoriasis is a multi-factorial heritable T-helper Th-1/Th-17 mediated inflammatory disease, affecting the skin. It is associated with co-morbidities such as Cardiovascular Disease (CVD). C-Reactive Protein (CRP) is a good inflammatory marker.

Endothelial nitric oxide synthase gene polymorphisms are associated with cardiovascular risks in prehypertensives.

Though endothelial nitric oxide synthase (eNOS) gene polymorphism is documented in the causation of hypertension, its role in prehypertension has not been investigated. The present study was conducted in 172 subjects divided into prehypertensives (n = 57) and normotensives (n = 115). Cardiovascular (CV) parameters including baroreflex sensitivity (BRS) by continuous BP variability assessment and sympathovagal imbalance (SVI) by heart rate variability analysis were recorded.

Relation between serum prolactin levels and antipsychotic response to risperidone in patients with schizophrenia.

Background: Hyperprolactinemia is commonly seen in patients with schizophrenia on risperidone. Dopamine receptor blockade plays a major role in risperidone induced hyperprolactinemia. However, limited studies are available with inconsistent results on antipsychotic response to risperidone and prolactin elevation.

Role of CYP2C19 gene polymorphism in acute alcohol withdrawal treatment with loading dose of diazepam in a South Indian population.

Purpose: Alcohol dependence is a public health problem worldwide, commonly associated with withdrawal symptoms for which diazepam is a frequently used drug. We studied the effect of CYP2C19 gene polymorphisms on diazepam loading dose requirement and time to reversal of acute alcohol withdrawal symptoms. We also studied the influence of the polymorphism in this gene on the persistent symptoms after loading dose of diazepam.

Pattern of Adverse Drug Reactions Reported with Cardiovascular Drugs in a Tertiary Care Teaching Hospital.

Background: Cardiovascular diseases (CVD) are one of the leading causes of non-communicable disease related deaths globally. Patients with cardiovascular diseases are often prescribed multiple drugs and have higher risk for developing more adverse drug reactions due to polypharmacy.

Aim: To evaluate the pattern of adverse drug reactions reported with cardiovascular drugs in an adverse drug reaction monitoring centre (AMC) of a tertiary care hospital.

A study to explore the correlation of ABCB1, ABCG2, OCT1 genetic polymorphisms and trough level concentration with imatinib mesylate-induced thrombocytopenia in chronic myeloid leukemia patients.

Purpose: Imatinib mesylate is presently the first-line treatment for chronic myeloid leukemia (CML). Therapeutic drug monitoring (TDM) and pharmacogenetic screening is warranted for better management of imatinib therapy. The present study was framed to explore the influence of common drug transporter gene polymorphisms of ABCB1, ABCG2, OCT1 and trough level concentration on commonly occurring adverse events in CML patients treated with imatinib mesylate.

Influence of Sokal, Hasford, EUTOS scores and pharmacogenetic factors on the complete cytogenetic response at 1 year in chronic myeloid leukemia patients treated with imatinib.

Imatinib mesylate is currently considered the first-line treatment for chronic myeloid leukemia (CML). Sokal, Hasford and EUTOS are the three major risk categorization scores available for CML patients. The present study aimed to explore the influence of three risk score, genetic polymorphisms of ABCB1, OCT1, ABCG2 and trough level concentration on complete cytogenetic response at 1 year and overall survival.

Prehypertension status, cardiometabolic risks, and decreased baroreflex sensitivity are linked to sympathovagal imbalance in salt-preferring individuals.

Salt preference has been reported to cause sympathovagal imbalance (SVI) and prehypertension. We investigated the role of inflammation, insulin resistance (IR), hyperlipidemia, and oxidative stress (OS) in genesis of SVI and cardiovascular (CV) risks in salt-preferring prehypertensives. The subjects were divided into no-salt-preferring (NSP, n = 87) and salt-preferring (SP, n = 89) group based on their preference for salted food.

Comparison of ranolazine and trimetazidine on glycemic status in diabetic patients with coronary artery disease - a randomized controlled trial.

Introduction: Cardiovascular diseases have become the leading cause of death around the globe and diabetes mellitus (DM) is considered to be a coronary artery disease (CAD) risk equivalent. Ranolazine, an anti anginal drug has been found to reduce Glycated haemoglobin (HbA1c) in diabetes patients with chronic angina. However the effect of another antianginal drug trimetazidine, on glycemic status is not clear.

Adverse drug reactions of imatinib in patients with chronic myeloid leukemia: A single-center surveillance study.

Objective: To monitor the adverse drug reactions (ADRs) associated with imatinib treatment in patients with chronic myeloid leukemia (CML) in a tertiary care hospital.

Materials And Methods: The study was carried out by the Departments of Pharmacology and Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India. The study was carried out from March 2012 to February 2014.

Association of CYP2C8, CYP2C9 and CYP2J2 gene polymorphisms with myocardial infarction in South Indian population.

Background: Cardiovascular diseases (CVDs) are the major cause of mortality and morbidity worldwide. Myocardial infarction (MI) is a complex multi-factorial, polygenic disorder arising from an interaction between genetic makeup of individuals and various environmental factors. CYP2C8, CYP2C9 and CYP2J2 gene involved in the metabolism of arachidonic acid, generates epoxyeicosatrienoic acids (EETs) that mediate dilation of coronary arteries improving post-ischemic cardiac contractile function, reduce vascular inflammation, and increase intravascular fibrinolysis.

An acenocoumarol dosing algorithm exploiting clinical and genetic factors in South Indian (Dravidian) population.

Objective: The objective of this study was to determine the influence of CYP2C9, VKORC1, CYP4F2, and GGCX genetic polymorphisms on mean daily dose of acenocoumarol in South Indian patients and to develop a new pharmacogenetic algorithm based on clinical and genetic factors.

Methods: Patients receiving acenocoumarol maintenance therapy (n = 230) were included in the study. Single nucleotide polymorphisms (SNP) of CYP2C9, VKORC1, CYP4F2, and GGCX were genotyped by real-time polymerase chain reaction (RT-PCR) method.

Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients.

Metformin is an oral antidiabetic drug, commonly used for treating type 2 diabetes mellitus (T2DM) patients. It is transported into the hepatocytes by polyspecific organic cation transporter 1, which is encoded by the gene SLC22A1. It has been hypothesized that genetic variations of SLC22A1 gene will influence inter-individual variation in glucose lowering efficacy of metformin.