ABSTRACT
CYP1A1 gene is involved in estrogen metabolism, and previously, we have reported association of variant rs2606345 with altered anti-epileptic drugs (AED) response in North Indian women with epilepsy (WWE). The present study aims to replicate the pharmacogenetic association, perform functional characterization and study its distribution within ethnically diverse Indian population. The variant was genotyped in 351 patients to assess the pharmacogenetic association and 552 healthy individuals belonging to 24 different ethnic groups to examine the distribution in Indian population. We observed significant overrepresentation of 'A' allele and 'AA' genotype in poor responders in WWE at Bonferroni-corrected significance levels. The recessive allele was found to lower the promoter activity by ~70-80% which was further substantiated by thermally less stable hairpin formed by it (ΔTm=7 °C). Among all ethnic groups, west Indo-European (IE-W-LP2) subpopulation showed highest genotypic frequency of the variant making women from this community more prone to poor AED response. Our results indicate that rs2606345 influences drug response in WWE by lowering CYP1A1 expression.
Subject(s)
Anticonvulsants/therapeutic use , Cytochrome P-450 CYP1A1/genetics , Epilepsy/drug therapy , Pharmacogenomic Variants , Adolescent , Adult , Anticonvulsants/adverse effects , Case-Control Studies , Cytochrome P-450 CYP1A1/metabolism , Epilepsy/enzymology , Epilepsy/ethnology , Epilepsy/genetics , Female , Gene Frequency , HEK293 Cells , Heterozygote , Homozygote , Humans , India/epidemiology , MCF-7 Cells , Male , Pharmacogenetics , Pharmacogenomic Testing , Phenotype , Promoter Regions, Genetic , Racial Groups/genetics , Recurrence , Transfection , Treatment Outcome , Young AdultABSTRACT
Depression is a common psychiatric illness and since majority of patients suffering from depression are first seen and treated by general practitioners, it is important for them to identify and treat depressive illness more effectively. Fortunately, depression is a treatable condition. Identifying the optimal antidepressant agent requires careful consideration of the patient's age, health status, and history of response to antidepressants. Other considerations include adverse effect profile, cost of drug therapy and convenient dosage schedule. Selective serotonin reuptake inhibitors are well tolerated and are considered by many to be the agents of choice in primary care treatment of depression because of their favourable adverse effect profile. Heterocyclic antidepressants are preferred in elderly patients and patients with medical problems. Tricyclic antidepressants can also be of great help specially to younger group of patients and patients who have failed to respond to other antidepressants.
