title: Genetic variation and haplotype structure of the gene Vitamin K epoxide reductase complex, subunit 1 in the Tamilian population.
abstract: OBJECTIVE
  To study the genetic variation and haplotype structure of Vitamin K epoxide reductase complex, subunit 1 (VKORC1) gene in the Tamilian population.
  
  
  METHODS
  The study was performed on 210 unrelated, healthy volunteers of the Tamilian population, of either sex between the age group of 18-60 years. Five ml of venous blood sample was collected using sodium ethylene diamine tetra acetic acid (EDTA) as anticoagulant. DNA was extracted using phenol-chloroform extraction method. Eight single nucleotide polymorphisms (SNPs) VKORC1 rs9923231 (G), rs7196161 (T), rs2884737 (T), rs17708472 (C), rs9934438 (C), rs8050894 (G), rs23596121 (C), and rs7294 (A) were studied using real-time quantitative Polymerase Chain Reaction (qPCR) method and they were included for constructing five-major haplotype blocks of VKORC1 gene.
  
  
  RESULTS
  The major alleles of VKORC1 rs9923231 (G), rs7196161 (T), rs2884737 (T), rs17708472 (C), rs9934438 (C), rs8050894 (G), and rs23596121 (C), were found to be at frequencies of 90.0%, 89.2%, 90.9%, 94.1%, 90.7%, 89.5% and 91.2%, respectively. The variant allele of VKORC1 rs7294 (A) was more frequent (83.6%) in the Tamilian population. The frequencies of haplotypes HAP1 (GTTCCGCA), HAP2 (ACGCTCTG), HAP3 (GTTTCGCG), HAP4 (GTTCCGCG) and HAP5 (GCTCCCCG) were found to be 80.0%, 7.4%, 4.7%, 1.5% and 1.1%, respectively.
  
  
  CONCLUSIONS
  In the present study the allele- frequency distributions, genotype and haplotype frequencies of the VKORC1 gene was considered. The findings of this study provide the genetic information required for learning the association of VKORC1 genetic variation and oral anticoagulant dose variability among patients receiving oral anticoagulants in the Tamilian population.
authors: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India.
authors: Dhakchinamoorthi Krishna
authors: DK
authors: Kumar
authors: Deepak Gopal
authors: DG
authors: Shewade
authors: Adithan
authors: A
authors: Surendiran
authors: Chandrasekaran
authors: C
authors: Adithan
keywords: Genotype; Vitamin K epoxide reductase complex subunit 1; haplotype
references: Blood Cells Mol Dis. 2011 Feb 15;46(2):147-50
references: 21185752
references: Genet Mol Res. 2012 Jan 09;11(1):70-6
references: 22290467
references: Pharmacogenomics. 2008 Sep;9(9):1237-50
references: 18781852
references: J Med Genet. 2006 Sep;43(9):740-4
references: 16611750
references: Biosci Trends. 2010 Dec;4(6):333-7
references: 21248432
references: Pharmacogenomics J. 2012 Aug;12(4):306-11
references: 21358752
references: Pharmacol Rep. 2010 Jul-Aug;62(4):740-6
references: 20885015
references: Bioinformatics. 2005 Jan 15;21(2):263-5
references: 15297300
references: Clin Pharmacol Ther. 2008 Feb;83(2):312-21
references: 17653141
references: Clin Pharmacol Ther. 2008 Sep;84(3):332-9
references: 18596683
references: Clin Pharmacol Ther. 2006 Oct;80(4):346-55
references: 17015052
references: BMC Med Genet. 2011 Jun 06;12:80
references: 21639946
references: Thromb Res. 2007;120(2):181-6
references: 17049586
references: Fundam Clin Pharmacol. 2012 Apr;26(2):295-306
references: 21265876
references: Pediatr Cardiol. 2006 Nov-Dec;27(6):685-8
references: 17031720
references: Nature. 2009 Sep 24;461(7263):489-94
references: 19779445
references: Blood. 2005 Oct 1;106(7):2329-33
references: 15947090
references: Mol Biol Rep. 2012 May;39(5):6343-51
references: 22318545
references: J Thromb Thrombolysis. 2008 Feb;25(1):45-51
references: 17906972
references: Pharmacogenet Genomics. 2011 Mar;21(3):130-5
references: 21228733
references: Thromb Haemost. 2005 Oct;94(4):773-9
references: 16270629
references: Clin Chim Acta. 2008 Oct;396(1-2):76-9
references: 18680736
references: Beijing Da Xue Xue Bao Yi Xue Ban. 2011 Dec 18;43(6):798-803
references: 22178823
references: Thromb Res. 2009 Jun;124(2):161-6
references: 19135231
references: Nature. 2004 Feb 5;427(6974):541-4
references: 14765195
references: Pharmacogenet Genomics. 2011 Jan;21(1):35-41
references: 21192345
references: Fundam Clin Pharmacol. 2005 Feb;19(1):101-5
references: 15660966
references: N Engl J Med. 2009 Feb 19;360(8):753-64
references: 19228618
references: Blood. 2005 Jul 1;106(1):135-40
references: 15790782
references: Pharmacogenomics. 2012 Feb;13(3):309-21
references: 22248286
references: N Engl J Med. 2005 Jun 2;352(22):2285-93
references: 15930419
references: Blood. 2010 May 6;115(18):3827-34
references: 20203262
references: Nature. 2004 Feb 5;427(6974):537-41
references: 14765194
references: Mol Pharmacol. 2009 Jun;75(6):1337-46
references: 19297519
references: Ann Hematol. 2011 Jun;90(6):635-41
references: 21110192
references: PLoS One. 2012;7(5):e37844
references: 22629463
references: J Thromb Thrombolysis. 2006 Dec;22(3):191-7
references: 17111199
references: Chest. 2001 Jan;119(1 Suppl):8S-21S
references: 11157640
references: Br J Clin Pharmacol. 2008 Feb;65(2):260-4
references: 17995970
references: Clin Pharmacol Ther. 2006 Apr;79(4):291-302
references: 16580898