title: Pharmacogenetic landscape of clopidogrel in north Indians suggest distinct interpopulation differences in allele frequencies.
abstract: OBJECTIVE
  Clopidogrel, a widely used antiplatelet drug, exhibits high interindividual variability; more than 80% of which could be explained by genetic polymorphisms. We built an allele frequency map of variants affecting clopidogrel response in north Indians.
  
  
  METHODS
  We mined a cross-sectional population-scale genome-wide dataset of 2128 Indo-Europeans residing in north India for presence of variants associated with pharmacogenetics of clopidogrel.
  
  
  RESULTS
  Our analysis reveals significant differences in population-scale allele frequencies between Indians and the global population. Indians had a higher allele frequency for variants in the CYP2C9*2, CYP2C9*3 and P2RY1 genes whereas lower frequency for the ABCB1, CYP1A2, CYP2C19*2C, CYP3A5 and PON1 genes compared with the global population. Furthermore, from our study we proposed a model to explain the higher prevalence of clopidogrel metabolizers in north Indians.
  
  
  CONCLUSIONS
  This is the largest population-scale genetic epidemiology study that provides a high-resolution map of variants associated with clopidogrel response that could be potentially valuable to clinicians to rationally plan appropriate dosage for therapy in resource poor conditions based on population level allele frequencies.
authors.affiliation: Genomics & Molecular Medicine Unit, CSIR-Institute of Genomics & Integrative Biology, Mathura Road, Delhi-110 020, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Giri
authors.forename: Nazir M
authors.initials: NM
authors.lastname: Khan
authors.forename: Analabha
authors.initials: A
authors.lastname: Basu
authors.forename: Nikhil
authors.initials: N
authors.lastname: Tandon
authors.forename: Vinod
authors.initials: V
authors.lastname: Scaria
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Bharadwaj
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000077144:Clopidogrel; D057225:Data Mining; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine