Background Coexisting polymorphisms of the genes affecting clopiogrel resistance may influence platelet activation. Methods and Results In 105 patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention, platelet function was measured and registered as closure time in the test with collagen and adenosine diphosphate (CADP-CT). Patients were followed for 12 months for death or recurrent myocardial infarction (MI). Genotyping revealed 7 carriers of both the C allele of P2Y12 and A allele of CYP2C19 (group 1), 14 carriers of the T allele of P2Y12 and A allele of CYP2C19 (group 2), 17 carriers of the C allele of P2Y12 and G allele of CYP2C19 (group 3) and 67 carriers of the T allele of P2Y12 and G allele of CYP2C19 (controls). The median CADP-CT value was significantly lower in group 1 than in group 2 or 3 (p<0.01) or controls (p<0.002), but did not differ between group 2 or 3 and controls. There were 2 cardiovascular deaths and 4 MI during follow-up, and the median CADP-CT value was lower in these patients (p=0.09). Conclusions Coexisting, rather then single, polymorphisms of different genes may be related to persistent platelet activation while on clopidogrel, which raises concern about harm in patients with ACS. (Circ J 2008; 72: 1165 - 1169)

Rationale:: Variants in TRIM63 , including a nonsense mutation (p.Q247X), have been suggested recently to cause hypertrophic cardiomyopathy. Objective:: To verify pathogenicity of TRIM63 p.Q247X detected by whole-exome sequencing in a symptomless professional sports player seeking medical advice because of a prolonged QT interval found during a routine check-up. Methods and Results:: Clinical studies were performed in the proband and his mother, who also carried TRIM63 p.Q247X. No evidence of hypertrophic cardiomyopathy was found in either person. Conclusions:: The p.Q247X variant in TRIM63 is not likely to be a highly penetrant variant causing hypertrophic cardiomyopathy.