title: Polymorphisms of MDR1, CYP2C19 and P2Y12 genes in Indian population: effects on clopidogrel response.
abstract: OBJECTIVE
  Influence of genetic variations on the response of clopidogrel, an antiplatelet drug is implicated. In the present study, the prevalence of single nucleotide polymorphisms of MDR1 (C3435T), CYP2C19 [CYP2C19*2 CYP2C19*3, CYP2C19*17] and P2Y12 (i-T744C) in Indian population and their effects on clopidogrel response was analyzed.
  
  
  RESULTS
  To analyze the prevalence of polymorphisms, 102 healthy individuals were recruited. Clopidogrel response was assessed by ADP induced platelet aggregation in clopidogrel naïve acute myocardial infarction (AMI) patients (n = 26) screened from 100 AMI cases, before loading dose of 300 mg, at 24 h before next dose and 6 days after on 75 mg per day and platelet aggregation inhibition (PAI) was calculated between these time intervals. Genotyping was carried out by PCR-based restriction enzyme digestion method for C3435T of MDR1 and i-T744C of P2Y12, by multiplex PCR for CYP2C19*2 (G681A) and CYP2C19*3 (G636A) and by nested PCR for CYP2C19*17 (C806T). The effect of the above mentioned genetic variations on PAI was analyzed. Variant allele of CYP2C19*3 was not observed while the prevalence of 3435T of MDR1 (0.524), CYP2C19*2 (681A, 0.352); i-744C of P2Y12 (0.088), as well as wild type allele CYP2C19*17 (C806, 0.897) associated with decrease clopidogrel response were observed. Trend toward poor response to clopidogrel was observed at 24 h with the variant genotypes of CYP2C19*2 and i-T744C of P2Y12 as compared to wild type.
  
  
  CONCLUSIONS
  The present study did show a trend toward impaired response of clopidogrel to inhibit platelet aggregation with variant genotypes of CYP2C19*2 and iT744C of P2Y12 compared to respective wild type genotype at 24 h.
authors: Research Scientist, Sir H.N. Medical Research Society, Sir H.N. Hospital and Research Centre, Raja Rammohan Roy Road, Mumbai, Maharashtra 400 004, India. Electronic address: Kavita_shalia@hnhospital.com.
authors: Kavita K
authors: KK
authors: Shalia
authors: Vinod K
authors: VK
authors: Shah
authors: Poonam
authors: P
authors: Pawar
authors: Siddhi S
authors: SS
authors: Divekar
authors: Satchidanand
authors: S
authors: Payannavar
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D044465:White People / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
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