title: Distribution of CYP2C19*17 allele and genotypes in an Indian population.
abstract: OBJECTIVE
  CYP2C19*17 allele increases the metabolic activity of CYP2C19 resulting in decreased therapeutic levels of CYP2C19 substrates. There exist inter-ethnic differences in the distribution of this allele. The present study was aimed at establishing the allele and genotype frequencies of CYP2C19*17 in a South Indian Tamilian population. Furthermore, we describe the haplotype structure of the three common variant alleles of CYP2C19 in the Tamilian population.
  
  
  METHODS
  Two hundred and six subjects of South Indian Tamilian origin were genotyped for CYP2C19*17 allele by nested polymerase chain reaction and restriction fragment length polymorphism. A subset of 87 subjects were also genotyped for CYP2C19*2 and CYP2C19*3 alleles. After ascertaining linkage disequilibrium (LD), haplotypes were constructed. Allele and genotype frequencies, LD pattern and haplotype frequency were compared with those of the HapMap populations.
  
  
  CONCLUSIONS
  The CYP2C19*17 allele frequency in the Tamilian population (n = 206) was found to be 19·2% (95% CI: 15·4 - 20·3). The CYP2C19*2 allele frequency (n = 87) was found to be 40·2% (95% CI: 32·9 - 47·5), whereas the CYP2C19*3 allele was not detected in the study subjects (n = 97). The high frequency of the CYP2C19*17 allele in the study population has resulted in a revision of frequencies for CYP2C19*1/*2 (31·0%) and CYP2C19*1/*1 (16·1%) genotypes in the Tamilian population. We also observed significant differences in haplotype structure and frequencies of these variant alleles in the HapMap population compared to Tamilian population.
  
  
  CONCLUSIONS
  CYP2C19*17 allele is present at high frequency in the Tamilian population. This study also demonstrates the need for reassessment of wild-type allele frequencies in view of CYP2C19*17 allele. The estimated high frequency of CYP2C19*17 allele will aid in genotype-phenotype association studies in the Tamilian population. Further genotype-phenotype association studies are required to evaluate the clinical utility of this allele in South Indians.
authors.affiliation: Department of Pharmacology, Pharmacogenomics Laboratory, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India.
authors.forename: D
authors.initials: D
authors.lastname: Anichavezhi
authors.forename: U S
authors.initials: US
authors.lastname: Chakradhara Rao
authors.forename: D G
authors.initials: DG
authors.lastname: Shewade
authors.forename: R
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: C
authors.initials: C
authors.lastname: Adithan
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics*; D001711:Biotransformation; D065731:Cytochrome P-450 CYP2C19; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19