RESUMO
BACKGROUND: Warfarin, an oral anticoagulant is used in patients who are at increased risk of developing blood clots. The management of warfarin therapy is challenging because it shows large inter and intra individual variability in patient response due to factors like age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORC1 genes. Studies implicate that polymorphisms in VKORC1 and CYP2C9 genes are associated with reduced doses of warfarin. The aim of our current study was to characterize the effects of VKORC1 and CYP2C9 gene variations that contribute to variability in warfarin dosing in Indian patients. METHODS: Genomic DNA was extracted from 103 patients undergoing warfarin therapy. Their mean daily warfarin dose, INR and demographics were recorded and genotyping of VKORC1 and CYP2C9 gene was performed by PCR-RFLP method. RESULTS: Individuals with wild type genotypes required highest mean warfarin dosage of 4.72 mg/day while VKORC1 variants required 3.6 mg/day to maintain their therapeutic INR. CYP2C9*2 genotype was not found to affect the warfarin maintenance dosages. The odds ratio for developing supra therapeutic INR in patients carrying VKORC1 variant allele when compared to wild types was 13.96 (95% CI; 4.85 - 44.65. Other factors affecting warfarin dosages were age and weight. CONCLUSION: Inclusion of pharmacogenetic data along with clinical parameters would help better predict warfarin doses in Indian patients.
Assuntos
Anticoagulantes/administração & dosagem , Hidrocarboneto de Aril Hidroxilases/genética , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/genética , Polimorfismo Genético , Vitamina K Epóxido Redutases/genética , Varfarina/administração & dosagem , Administração Oral , Adulto , Idoso , Anticoagulantes/metabolismo , Hidrocarboneto de Aril Hidroxilases/metabolismo , Distribuição de Qui-Quadrado , Citocromo P-450 CYP2C9 , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos , Feminino , Genótipo , Humanos , Índia , Coeficiente Internacional Normatizado , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Farmacogenética , Fenótipo , Vitamina K Epóxido Redutases/metabolismo , Varfarina/metabolismoRESUMO
OBJECTIVES: CF, caused due to abnormal transport of chloride, sodium and bicarbonate ions across epithelial cell membranes, is a multi-organ disorder. More than 1000 mutations causing CF, have been identified in the CFTR gene, of which AF508 is the most severe, predominant mutation. However, data on CF in India is limited. Also, facilities for CF diagnosis are not available at all diagnostic centres across India. RESULTS: AF508 mutation has been reported in 19-56% Indian patients. Also, the spectrum of mutations has been anticipated to be different, due to the identification of a wide range of novel and rare mutations. In addition to mutations, polymorphisms with clinical relevance and practical diagnostic value have also been identified. Clinical profile in Indian patients was also observed to be different. CONCLUSION: Though, Cystic Fibrosis has always been considered to be a rare disease in India, we hope that the identification of the wide range of mutations, leads us to the recognition of a probable increased incidence of CF in Indian patients. And this would attract greater attention to the diagnosis of this disease, so that a clinically appropriate assay can be developed for their detection as a preliminary test for CF diagnosis. The results observed during the study can be a step forward in planning a molecular screening and providing appropriate genetic counseling programs, which are lacking in our country at the moment.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Mutação/genética , Polimorfismo Genético , Fibrose Cística/diagnóstico , Humanos , ÍndiaRESUMO
Background. Metabolic syndrome (MS) is characterised by a constellation of individual risk factors of cardiovascular disease. Materials and Methods. The current study was a population-based survey of cohort of subjects in the metropolitan city of Mumbai. A total of 548 subjects, who attended the CARDIAC evaluation camp, were recruited in the study. Participants with complete fasting lipid profiles, blood glucose, and known cardiac risk markers were evaluated. Results. On applying modified NCEP ATP III, we found out that nearly 95% of the subjects had at least one abnormal parameter. We found the prevalence of MS in our study population to be 19.52%. The prevalence of MS in males was almost double than females (P = .008). The overall prevalence of BMI (>23 kg/m(2)) was 79.01%. Increased hypertriglyceridemia and decreased levels of HDL-C were found to be more in males (P < .0001). Conclusion. The low percentage of subjects with normal and controlled parameters suggests that there is a need for awareness programs and lifestyle interventions for the prevention and control of MS.
