Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin.

Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Abstract Text:

Qing Li,Bi-Lian Chen,Vural Ozdemir,Wei Ji,Yan-Mei Mao,Lian-Ci Wang,Hei-Ping Lei,Lan Fan,Wei Zhang,Jie Liu,Hong-Hao Zhou,Qing Li,Bi-Lian Chen,Vural Ozdemir,Wei Ji,Yan-Mei Mao,Lian-Ci Wang,Hei-Ping Lei,Lan Fan,Wei Zhang,Jie Liu,Hong-Hao Zhou,

BACKGROUND: Aspirin is a frequently prescribed drug for primary and secondary prevention of myocardial infarction, stroke and cardiovascular death. However, aspirin resistance may affect up to 45% of the population. Little is known on the role of genetic factors that contribute to resistance or augmented response to aspirin in different human populations. METHODS: In a large sample of nonsmoker, medication-free healthy volunteers from mainland China (n = 323; age: 22.1 +/- 2.0 years) (mean +/- standard deviation), we determined the frequency of polymorphisms in cyclooxygenase 1 (COX1) (A-842G and C50T), glycoprotein IIIa (GPIIIa) (PLA1/A2) and purinergic receptor P2Y (P2Y1) (C893T and A1622G) genes. These candidate genes were chosen on the basis of their impact on platelet physiology and aspirin mode of action. A four panel P2Y1 genotype-stratified sample of healthy volunteers (n = 24 in total), identified from the large study sample above, prospectively received a 100 mg daily oral dose of aspirin for 7 days. We measured changes in platelet aggregation before and after aspirin treatment. As a comparison reference group, 6 out of 24 subjects in the prospective aspirin trial had the P2Y1 CT893/AG1622 genotype that displays a low frequency (<7%) in the Chinese population. RESULTS: COX1 A-842G, C50T and GPIIIa PLA1/A2 genetic polymorphisms were not observed in our sample from mainland China. Allele frequencies of P2Y1 893T and 1622G were 3.5 and 30.6%, respectively. The heterozygosity for the P2Y1 A1622G polymorphism observed in the present study was different to Caucasians; Chinese displayed a higher allele frequency for the 1622G allele. After aspirin treatment, the net decrease in arachidonic acid-induced platelet aggregation was significantly larger in the P2Y1 CT893/AG1622 genotype panel (83.4 +/- 3.7%, net reduction by aspirin expressed as percentage of baseline) compared with CC893/GG1622 (68.2 +/- 13.5%), CC893/AG1622 (68.9 +/- 9.6%) and CC893/AA1622 (65.1 +/- 9.1%) genotypic groups (p = 0.012, 0.025 and 0.004, respectively; statistical power = 77%). There was no significant difference in antiplatelet effect of aspirin among the CC893/GG1622, CC893/AG1622 and CC893/AA1622 genotypes (p > 0.05). CONCLUSIONS: The COX1 A-842G, C50T and GPIIIa PLA1/A2 polymorphisms are rare in Chinese. In contrast to previous studies in Caucasian populations, these candidate functional polymorphisms are unlikely to be significant contributors to aspirin pharmacodynamics in Chinese persons. Importantly, the presence of the P2Y1 893CC genotype appears to confer an attenuated antiplatelet effect during aspirin treatment in healthy Chinese volunteers. These data collectively underscore the importance of population-to-population variability in clinical pharmacogenetics research and provide a basis for further long-term studies of aspirin response and P2Y1 genetic variation in patients with cardiovascular risk.

Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Publishing Authors By Initials

Q Li,BL Chen,V Ozdemir,W Ji,YM Mao,LC Wang,HP Lei,L Fan,W Zhang,J Liu,HH Zhou,Q Li,BL Chen,V Ozdemir,W Ji,YM Mao,LC Wang,HP Lei,L Fan,W Zhang,J Liu,HH Zhou,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Pharmacogenomics

VOLUME: 8

Page Numbers: 577-86

Journal Abbreviation: Pharmacogenomics

ISSN: 1744-8042

DAY: 11

MONTH: Jun

YEAR: 2007

Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100897350

Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin.

AFFILIATION: Central South University, Institute of Clinical Pharmacology, Pharmacogenetics Research Institute, Changsha, Hunan 410078, China.

Country: England

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Pharmacogenomics

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese population and association with attenuated response to aspirin Related Publications

• Inhibitors of Na+/H+ and Na+/Ca2+ exchange depress intracellular calcium elevation induced by ischemia/reperfusion in rat cardiac myocytes.
• Inhibitory effect of recombinant FN polypeptide CH50 on the metastasis and tumor growth.
• Quantification of bcr/abl mRNA expression level in leukemia cells by FQ-RT-PCR.
• [An experimental study on the survival of the anterior abdominal skin flap after VEGF cDNA administration]
• [An inquiry into blood loss in laparoscopic liver resections]
• [Association studies of dopamine D4 receptor gene and dopamine transporter gene polymorphisms in Han Chinese patients with attention deficit hyperactivity disorder]
• [Beneficial effect of thyrotropin-releasing hormone in combination with HSD on hemorrhagic shock with pulmonary edema at high altitude in the rat]
• [Changes in platelet membrane glycoprotein levels in patients with cardiopulmonary resuscitation]
• [Clinical analysis of 13 infected total knee replacements]
• [Detection of epileptic waves in EEG based on wavelet transform]
• [Effects of Alexandrium tamarense and Prorocentrum donghaiense on rotifer Brachionus plicatilis population]
• [Effects of the novel gene, LAPTM4B, highly expression in hepatocellular carcinoma on cell proliferation and tumorigenesis of NIH3T3 cells]
• [Experimental study of K562 cell apoptosis induced by harringtonine]
• [Expression of otsA gene in tobacco and improvement stress tolerance]
• [Hemodynamic and pathologic changes in open abdominal wound after seawater immersion in dog]
• [High efficient expression of recombinant human platelet factor IV in pichia pastoris]
• [Identification of radix Rubiae and the root of Humulus scardens (Lour.) Merr.]
• [Incompatibility among indigenous plasmids of Sinorhizobium fredii strains and its application for plasmid curing]
• [Nutrition support of severe illness patients of general surgery during perioperation period]
• [Preliminary analysis of the characteristics of red tide areas in Changjiang River estuary and its adjacent sea]
• [Relationship between tissue inhibitors of metalloproteinase and metastasis and prognosis in breast cancer]
• [Repairing large alar defects by using a retro-grade auricular flap]
• [Research advance in effects of harmful algal bloom species on zooplankton]
• [Scoring protocol for quantitative diagnosis of gastrointestinal dysfunction and failure in severe cases]
• [Study on new techniques for genetic diagnosis of deletional alpha-thalassemia]
• [The influence of intrahepatic transplantation of hepatocytes and insular cells on liver cirrhosis]
• [The relationship of facet orientation to intervertebral disc protrusion and lateral recess stenosis in lower lumbar spine]
• [Transplantation of bone marrow cells upregulated vascular endothelial growth factor and its receptor and improved ischemic myocardial function]
• [Ultrasound surveillance of cervical lymph node metastasis in thoracic esophageal carcinoma]
• [Using scar tissue flap to repair secondary nasal deformities of unilateral cleft lip]