title: Polymorphic genetic variations of cytochrome P450 19A1 and T-cell leukemia 1A genes in the Tamil population.
abstract: Aromatase inhibitors (AIs) are anti-neoplastic drugs widely used for the treatment of endocrine responsive breast carcinoma in postmenopausal women. Drug disposition, efficacy and tolerability of these agents are influenced by germ-line polymorphisms in the sequence of the genes encoding CYP19A1 and TCL1A proteins. In the current work, we aimed to determine the haplotype structures, linkage disequilibrium (LD) patterns, and allele and genotype frequency distribution of pharmacologically important variants from two genes (CYP19A1 and TCL1A) in Tamil population and assessed their ethnic differences. DNA derived from peripheral leukocytes of 111 healthy subjects were genotyped for 15 pharmacogenetic variants by real time thermocycler through allelic discrimination method using TaqMan 5' nuclease genotyping assay. The polymorphic variant allele frequencies of CYP19A1 were 42.3% (rs4646, T), 18% (rs10046, T), 36% (rs700519, T), 16.7% (rs700518, G), 26.1% (rs727479, G), 18% (rs4775936, T), 32% (rs10459592, G), 15.3% (rs1062033, C), 33.8% (rs749292, A), 40.1% (rs6493497, T) and 40.1% (rs7176005, G). TCL1A gene allele frequencies were 26.1% (rs7158782, G), 27% (rs7159713, G), 21.2% (rs2369049, G) and 27.5% (rs11849538, G). Comparing our data across the 5 HapMap populations (CEU, GIH, HCB, JPT and YRI) huge inter-ethnic differences were exhibited in the variant allele frequencies, LD patterns and haplotype blocks. Our results emphasize the importance of normative frequency documentation and will offer significant clinical relevance in personalizing AIs therapy.
authors.affiliation: ICMR Centre for Advanced Research in Pharmacogenomics, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India. Electronic address: umagenes@gmail.com.
authors.forename: Gurusamy
authors.initials: G
authors.lastname: Umamaheswaran
authors.affiliation: Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
authors.forename: Dharanipragada
authors.initials: D
authors.lastname: Kadambari
authors.affiliation: ICMR Centre for Advanced Research in Pharmacogenomics, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
authors.forename: Annan Sudarsan Arun
authors.initials: AS
authors.lastname: Kumar
authors.affiliation: Department of Biotechnology and Biochemical Engineering, Sree Buddha College of Engineering, Alappuzha 690529, Kerala, India.
authors.forename: Mohan
authors.initials: M
authors.lastname: Revathy
authors.affiliation: Department of Biotechnology and Biochemical Engineering, Sree Buddha College of Engineering, Alappuzha 690529, Kerala, India.
authors.forename: Raj
authors.initials: R
authors.lastname: Anjana
authors.affiliation: ICMR Centre for Advanced Research in Pharmacogenomics, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
authors.forename: Chandrasekaran
authors.initials: C
authors.lastname: Adithan
authors.affiliation: ICMR Centre for Advanced Research in Pharmacogenomics, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
authors.forename: Steven Aibor
authors.initials: SA
authors.lastname: Dkhar
mesh_terms: D001141:Aromatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human; D001141:Aromatase; C561410:CYP19A1 protein, human
keywords: Aromatase inhibitor; CYP19A1; Haplotypes; Inter-ethnic variation; TCL1A; Tamil population