The Correlation Between MDR1 Gene Polymorphism and Clopidogrel Resistance in People of the Hui and Han Nationalities
Jing Zhang1, Zhi-Feng Dong2, Cheng-Xue Bian3
1Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Yantai, China.
Insights
The multidrug resistance protein 1 (MDR1) C3435T polymorphism is linked to clopidogrel resistance in patients undergoing percutaneous coronary intervention (PCI). The T allele increases resistance risk, with no significant nationality-based differences observed for this specific polymorphism.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Genetics
Background:
- Clopidogrel is a crucial antiplatelet medication used after percutaneous coronary intervention (PCI).
- Individual responses to clopidogrel can vary, partly due to genetic factors influencing drug metabolism and efficacy.
- Multidrug resistance protein 1 (MDR1), also known as ABCB1, plays a role in drug transport and may affect clopidogrel response.
Purpose of the Study:
- To investigate the association between MDR1 (ABCB1) gene polymorphisms and clopidogrel resistance in Hui and Han Chinese patients post-PCI.
- To compare the prevalence of clopidogrel resistance and relevant genetic variations between the Hui and Han ethnic groups.
Main Methods:
- A cohort of 377 patients (154 Hui, 223 Han) who underwent PCI was studied.
- Platelet aggregation was measured using light turbidimetry after adenosine diphosphate induction.
- Restrictive fragment-length polymorphism polymerase chain reaction was used to genotype MDR1 C3435T and C1236T loci.
Main Results:
- The overall incidence of clopidogrel resistance was 23.4%.
- Patients with the TT genotype and T allele at the MDR1 C3435T locus showed significantly higher rates of clopidogrel resistance (P < 0.05).
- No significant differences in C3435T genotype or allele frequencies were found between Hui and Han nationalities, but C1236T distribution differed significantly (P < 0.05).
Conclusions:
- The T allele of the MDR1 C3435T polymorphism is a significant predictor of clopidogrel resistance in PCI patients.
- Genetic variations in MDR1 C3435T do not appear to differ significantly between Hui and Han populations in relation to clopidogrel resistance.
- Further research may explore ethnic-specific responses to antiplatelet therapies.
Abstract:
To investigate the differences in the correlation between multidrug resistance protein 1 (MDR1) (ABCB1) gene polymorphism and clopidogrel resistance in patients of the Hui and Han nationalities with percutaneous coronary intervention (PCI). A total of 377 subjects (154 people of Hui nationality, 223 people of Han nationality) with PCI were enrolled in the study. Each patient's platelet aggregation rate was induced by adenosine diphosphate and measured using light turbidimetry. Based on the results, the patients were divided into two groups: a clopidogrel resistance (CR) group and a non-clopidogrel resistance (NCR) group. Restrictive fragment-length polymorphism polymerase chain reaction technology was then used to determine the genotype and alleles at two loci (C3435 T[rs1045642] and C1236 T[rs1128503]), calculate the frequencies of the genotype and alleles at these two loci, and conduct correlation analysis. The incidence rate of clopidogrel resistance was 23.4%, and the frequencies of the TT genotype and T allele at C3435 T for patients of both nationalities were significantly higher in the CR group than in the NCR group (P < 0.05). There were no significant differences between the two groups in genotype or allele frequency at C1236 T. There was a significant difference in the distribution of C1236 T polymorphism between the two nationalities (P < 0.05), but there was no significant difference between the two nationalities in C3435 T polymorphism. Patients with a T allele at MDR1 C3435 T are more likely to show clopidogrel resistance, and no significant differences were identified in C3435 T gene polymorphism between the two nationalities.
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