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The Relationship of Platelet Cyclooxygenase-1 Gene A-842G Single Nucleotide Polymorphism and Aspirin Resistance

Author: WangZhongLiang
Tutor: LiuKeQiang
School: Tianjin Medical University
Course: Internal Medicine
Keywords: aspirin resistance cyclooxygenase-1 gene single nucleotide polymorphism platelet aggregation urinary 11-dehydro-Thromboxane B2 clopidogrel
CLC: R541.4
Type: Master's thesis
Year: 2007
Downloads: 157
Quote: 1
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Abstract

Objective The study was designed to investigate the clinical factors of aspirin resistance and the relationship of the cyclooxygenase-1 gene A-842G single nucleotide polymorphism and aspirin resistance.To clarify molecular biological mechanism of AR and offer the strategy for identifing and dealing with the clinical AR.Methods①136 patients（Han people） with stable angina pectoris, 69of them are men, 67 are women, their ages are from 35 to 75, the average age is 61.43±8.92 years. They were placed on aspirin 100 mg/day≥7days, 31 patients（Han people） with acute coronary syndrome, 20 of them are men, 11are women, their ages are from 40 to 75, the average age is 62.93±7.02 years. They were placed on both aspirin 100 mg/day≥7days and clopidogrel 75 mg/day≥7days, platelet aggregation percentage by adenosine diphosphate induction and urinary 11-dehydro-Thromboxane B₂ levels by ELASA method were conducted for 167 patients when they were hospitalized and after taking medicine for 7 days. The COX-1 A-842G single nucleotide polymorphism were examined by PCR.②The 136 patients placed on aspirin only were devided into aspirin resistance（AR） and aspirin sensitive（AS）group based on platelet aggregation rate after taking medicine for 7 days. Age、systolic pressure、diastolic pressure, fasting blood glucose、PLT、BUN、HDL、LDL、WBC、RBC、gender、diabetes were compared between the two groups; urinary 11-dehydro-Thromboxane B₂ levels were compared between the AR and AS groups before and after taking medicine, AG、GG and AA genotype frequency were analized between the two groups to clarified the relationship between COX-1 A-842G SNP and aspirin resistance.③Platelet aggregation percentage and urinary 11-TXB₂ compared between the group placed on aspirin only and the one on aspirin and clopidogrel before and after taking medicine, in order to establish the strategy of prevention from AR by using the synergy of aspirin and clopidogrel.④The main clinical cardiovascular events rate in two weeks were compared between AR and AS groups.⑤The statistical analysis of the enumeration data was used by chi square test and the comparison of the means of two groups was by independent sampler t-test. All statistical analysis were made by the software of spss 11.5. P＜0.05 and P＜0.01 show significant diference.Results①Using the platelet aggregation rate≥70% as the cut-off point between AR and AS, respectively76.87±3.33 and 39.42±6.78（p＜0.01 ）, 10.2% of the 136 patients taking aspirin alone were AR and none of the 31 patients taking both aspirin and clopidogrel showed aspirin resistance（32.66±5.74）; the levels of urine 11-DH-TXB₂ of urine in AR group were higher than the AS group after taking medicine（p＜0.01）; The frequency of AG+GG genotype of COX-1 was 50%in AR group and 15.57% in AS group（p＜0.05）; The frequency ofG genotype（AG+GG） was 26.92% and 17.27%（AA）in AR（p＜0.05） baced on the G genotype to divide the group.②The platelet aggregation of AG+GG genotype group was higher than the AA group before and after taking medicine（respectively p＜0.05）, the decreased levelof the platelet aggregation and urinary 11-DH-TXB₂ were higher in AG+GG genotype group after taking medicine（p＜0.05）.③Only the LDL in AR patients was higher than that in AS patients（p＜0.05）.④The platelet aggregation and urinary 11-DH-TXB₂ in taking both aspirin and clopidogrel group were higher than those in taking aspirin alone group before taking medicine（respectively p＜0.05、p＜0.01）, the decreased level of platelet aggregation and urinary 11-DH-TXB₂ were higher in two drugs group than those in one drug group（respectively p＜0.01）.⑤The event rate in AR group was higher than that in AS group（35.71%vs10.66%, p＜0.05）Conclusion①cox-1 A-842G single nucleotide polymorphism may be related to AR, the patients with AG+GG genotype may prone to AR.③aspirin pluse clopid0grel can decrease the platelet aggregation rate and urinary 11-DH-TXB₂ obviously. It may prevent frorn AR.④LDL may be related to AR, the patients with the higher level of LDL may prone to AR.②the patients with AR had a higher cardiovascular event rate.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Coronary arteries ( atherosclerosis ),heart disease (CHD)
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