Disease Information

General Information of the Disease (ID: DIS00270)

• Name: Cerebral ischaemic stroke
• ICD: ICD-11: 8B11

Type(s) of Resistant Mechanism of This Disease

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Clopidogrel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Cytochrome P450 family 1 subfamily A member 1 (CYP1A1) [1]

• Resistant Disease: Acute Ischemic Stroke [ICD-11: 8B11.0]
• Resistant Drug: Clopidogrel
• Molecule Alteration: Missense mutation; CYP3A5 (rs776746) GG + AG and CYP2C19*2 (rs4244285) AA + AG genotypes
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Matrix-assisted laser desorption/ionization time of flight mass spectrometry assay
• Experiment for Drug Resistance: Platelet aggregation test assay
• Mechanism Description: The estimated risk of clopidogrel resistance was significantly higher in patients with CYP3A5 (rs776746) GG and CYP2C19*2 (rs4244285) AA, as compared to patients harboring CYP3A5 (rs776746) AA and CYP2C19*2 (rs4244285) GG. These data suggest that these two CYP genetic variants together significantly contributed to clopidogrel resistance. The relative risk conferred by the combinations of CYP3A5 GG and CYP2C19*2 AA was considered as a high-risk variable, with assigned as one, and other combinations of CYP3A5 and CYP2C19*2 as a low-risk variable, with assigned as zero.

References

• Ref 1: Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke .J Atheroscler Thromb. 2016 Oct 1;23(10):1188-1200. doi: 10.5551/jat.33290. Epub 2016 Mar 8. 10.5551/jat.33290