Publications (2)3.96 Total impact
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Article: Haplotype structures of common variants of CYP2C8, CYP2C9, and ADRB1 genes in a South Indian population.
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ABSTRACT: In association with candidate genes, the observed trait may be due to either one of the variant alleles or the interaction of variant alleles at different loci, which are in linkage disequilibrium. The objective of this study was to investigate the baseline allele and genotype frequencies, linkage disequilibrium (LD) patterns, and haplotype structures of common variants of the CYP2C8, CYP2C9, and ADRB1 genes located on chromosome 10. Two hundred and forty-five healthy subjects were recruited from South India and were compared with the HapMap Project's population for LD pattern, allele and genotype frequencies, and haplotype structures. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism and TaqMan assay on real-time polymerase chain reaction. A significant ethnic difference was found in the LD patterns among the variant alleles between the South Indian population and other major ethnic groups, namely African, European, Chinese, and Japanese. This study established the normative allele and genotype frequencies, haplotype structure, and LD patterns of common variants of the CYP2C8, CYP2C9, and ADRB1 genes in a South Indian population (Tamilian). The data may be helpful to plan candidate gene-trait association studies in this population.Genetic Testing and Molecular Biomarkers 03/2011; 15(6):407-13. · 1.11 Impact Factor -
Article: Influence of CYP2C9 and CYP2C19 genetic polymorphisms on phenytoin-induced neurological toxicity in Indian epileptic patients.
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ABSTRACT: Cytochrome P450 2C9 and 2C19 (CYP2C9 and CYP2C19, respectively) genetic polymorphisms play an important role in phenytoin (PHT) metabolism. We have evaluated whether these genetic polymorphisms have an effect on PHT-induced neurological toxicity in Tamilian (ethnic group native to southern India) patients with epilepsy. We studied 292 Tamilian patients who were taking PHT for the treatment of various epileptic seizures. PHT toxicity was defined on the basis of neurological signs of toxicity and further sub-classified into mild, moderate, and severe toxicity based on clinical severity. Genomic DNA was extracted from peripheral leukocytes and genotyped for CYP2C9*2, *3 and CYP2C19*2, *3 by PCR-restriction fragment length polymorphism analysis. Of the 292 patients in the patient cohort, 58 were clinically diagnosed to have PHT toxicity. When risk ratios were calculated for each mutant CYP2C9 genotype separately, the adjusted odds ratio for CYP2C9*1/*3 was found to be 15.3 (95% confidence interval 5.8-40.3, P<0.0001) for the cases compared to controls. When the four single nucleotide polymorphisms of CYP2C9 and CYP2C19 were analyzed using a haplotype approach, significant difference in the distribution of the C-C-G-G haplotype was observed between the cases and controls. Our results show that CYP2C9 genetic polymorphisms (particularly the *3 allele) were associated with high risk of epileptic patients developing PHT-induced neurological toxicity.European Journal of Clinical Pharmacology 04/2010; 66(7):689-96. · 2.85 Impact Factor
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Institutions
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2010
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Jawaharlal Institute of Postgraduate Medical Education & Research
- Department of Pharmacology
Pondicherry, Union Territory of Puducherry, India
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