Ethnic differences in allele, genotype distributions and lung cancer risk of polymorphisms of gemcitabine metabolic pathway genes in south Indian population

Background: Gemcitabine is a widely used cytotoxic drug in the treatment of a number of solid tumors, for instance, lung, pancreatic as well as breast cancer. As a consequence of the progressive genomic instability, the efficiency rates have eventually lowered. Genetic approach targeting one or several genes in drug targeting pathways facilitates substantially more valuable details in explaining the association between variants and also the efficacy of gemcitabine therapy. In addition, several researchers have reported ethnic discrepancies in clinical response to gemcitabine. Thus, the present study was aimed to establish the normative frequencies of genes associated with the metabolic pathway of Gemcitabine (RRM1 -37C>A (rs12806698), RRM1 -524T>C (rs11030918), CDA 79A>C (rs2072671) and CDA 435 C>T (rs1048977) in South Indian healthy population and compared with 1000 genome population. Additionally, the association of these SNPs with the risk of developing lung cancer was also evaluated.Methods: This study was carried out on 184 healthy subjects and 123 lung cancer patients of South Indian origin and genotyping was done using RT-PCR (Real Time Polymerase Chain Reaction). The frequencies of the above polymorphisms were in Hardy-Weinberg equilibrium (p >0 .05).Results: The minor allele frequencies of the SNPs RRM1 -37C>A (rs12806698), RRM1 -524T>C (rs11030918), CDA 79A>C (rs2072671) and CDA -435 C>T (rs1048977) were 31.3, 36.7, 24.5 and 22.0 respectively.Conclusions: There was a significant difference observed between the genotype and allele frequencies of south Indians with the 1000 genome populations. We also found that SNPs of RRM1 were significantly associated with lung cancer risk

Pattern of use of antibiotics in hospitalized patients in the medicine department of a tertiary care hospital

Background: (1) To assess pattern of antibiotic use among in-patients of medicine unit in a tertiary care hospital, (2) to determine the frequency of adverse drug reactions (ADR) among the inpatients receiving antibiotics in medicine unit.Methods: The study was prospective and based on the daily review of patient records for 2 months (June, July) of study period, including all the inpatients of medicine unit 1 receiving antimicrobials. The general information of the patients, infection, antimicrobial use, culture and sensitivity reports, concomitant disease, concomitantly administered drugs, as well as clinical response were collected. The prescribed antimicrobials were correlated with the patient’s culture and sensitivity report. The number of defined daily doses (DDDs) administered per patient was calculated for each antimicrobial prescribed as per WHO anatomical therapeutic chemical classification. The ADR observed during the study were assessed using WHO causality analysis. The economic burden of the antimicrobial used was analyzed using average cost of antimicrobial per patient. The study was approved by the Institute Ethics Committee.Results: The antimicrobials that are commonly used as per total drug use (DDDs) are ceftriaxone followed by doxycycline and metronidazole. The antimicrobials account for 58.6% of cost spent on drugs for inpatients. Four antimicrobial related ADR were reported during the study period.Conclusion: Ceftriaxone, doxycycline, and metronidazole are commonly used antibiotics and significant proportion of the cost of drugs is spent for antimicrobials in a medicine unit

Influence of ABCB1 genetic polymorphisms on the antiemetic response to ondansetron-based medication for cisplatin-based chemotherapy in South Indian cancer patients in a tertiary care hospital

Genetic variations in the receptor, metabolizing enzymes and transporters may explain a part of the variation in anti-emetic response to ondansetron among cancer patients. This study assesses the role of ABCB1 genetic polymorphisms in the anti-emetic efficacy of ondansetron-based medication for cisplatin-based chemotherapy in South Indian cancer patients

Relative Copy Number Variations of CYP2C19 in South Indian Population

CYP2C19 is a polymorphic enzyme involved in the metabolism of clinically important drugs. Genotype-phenotype association studies of CYP2C19 have reported wide ranges in the metabolic ratios of its substrates. These discrepancies could be attributed to the variations in the promoter region and this aspect has been reported recently. The observations in the recent reports on the influence of promoter region variants on the metabolism of CYP2C19 substrates might also have been influenced by the copy number variations of CYP2C19. In this paper, we describe copy number variations of CYP2C19 using real-time polymerase chain reaction by comparative Ct method. No copy number variations were observed in the south Indian population indicating the observed discrepancies in genotype-phenotype association studies might be due to the regulatory region polymorphisms as reported earlier

Dopamine ( DRD2 ) and Serotonin ( HTR2A, 2C) Receptor Gene Polymorphisms do not influence early response to Risperidone in South Indian Patients with Schizophrenia

International audienc

Risperidone response in patients with schizophrenia drives DNA methylation changes in immune and neuronal systems

International audienceBackground: The choice of efficient antipsychotic therapy for schizophrenia relies on a time-consuming trial-and-error approach, whereas the social and economic burdens of the disease call for faster alternatives. Material & methods: In a search for predictive biomarkers of antipsychotic response, blood methylomes of 28 patients were analyzed before and 4 weeks into risperidone therapy. Results: Several CpGs exhibiting response-specific temporal dynamics were identified in otherwise temporally stable methylomes and noticeable global response-related differences were observed between good and bad responders. These were associated with genes involved in immunity, neurotransmission and neuronal development. Polymorphisms in many of these genes were previously linked with schizophrenia etiology and antipsychotic response. Conclusion: Antipsychotic response seems to be shaped by both stable and medication-induced methylation differences