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Articles by P. A Peyser
Total Records ( 2 ) for P. A Peyser
  Y. V Sun , P. A Peyser and S. L.R. Kardia
 

Background— Previous studies indicate that the endothelin system is involved in hypertension, heart failure, atherosclerosis, chronic kidney disease, and diabetes. To explore the potential genetic effects of copy number variations (CNVs) on the endothelin system, which underlie these diseases, we studied the association of genome-wide CNVs with gene expression levels of 7 genes involved in the endothelin system using independent HapMap subjects including 90 Asians (45 Han Chinese and 45 Japanese), 60 whites, and 60 blacks.

Methods and Results— For each subject, the genome-wide variations were measured using the Affymetrix 6.0 chip that includes measurements of 906 000 single-nucleotide polymorphisms and 946 000 CNV probes. The gene expression profiles of the transformed B lymphocytes were measured for the same subjects. Among the 210 subjects, we identified 1529 CNV regions on 22 autosomes. By testing the association between CNVs and the gene expression levels in each racial group using linear regression, we identified 4 statistically significant CNV associations in all 3 groups (=0.05). The strongest association was between a 66 kbp CNV region located on chromosome 6 and endothelin-1 (EDN1) expression. The effects of the CNV-EDN1 association in the 3 racial groups were in the same direction and explained 7% to 14% of the variation in EDN1 expression.

Conclusions— Although the biological function of the chromosome 6 CNV is unclear, the significant and consistent association found in 3 racial groups suggests that CNVs may contribute to variation in underlying risks of common disease through their effects on key molecular signaling pathways.

  K Musunuru , W. S Post , W Herzog , H Shen , J. R O'Connell , P. F McArdle , K. A Ryan , Q Gibson , Y. C Cheng , E Clearfield , A. D Johnson , G Tofler , Q Yang , C. J O'Donnell , D. M Becker , L. R Yanek , L. C Becker , N Faraday , L. F Bielak , P. A Peyser , A. R Shuldiner and B. D. Mitchell
  Background—

Genome-wide association studies have identified a locus on chromosome 9p21.3 to be strongly associated with myocardial infarction/coronary artery disease and ischemic stroke. To gain insights into the mechanisms underlying these associations, we hypothesized that single nucleotide polymorphisms (SNPs) in this region would be associated with platelet reactivity across multiple populations.

Methods and Results—

Subjects in the initial population included 1402 asymptomatic Amish adults in whom we measured platelet reactivity (n=788) and coronary artery calcification (CAC) (n=939). Platelet reactivity on agonist stimulation was measured by impedance aggregometry, and CAC was measured by electron beam CT. Twenty-nine SNPs at the 9p21.3 locus were genotyped using the Affymetrix 500K array. Twelve correlated SNPs in the locus were significantly associated with platelet reactivity (all P≤0.001). The SNP most strongly associated with platelet reactivity, rs10965219 (P=0.0002), also was associated with CAC (P=0.002) along with 9 other SNPs (all P<0.004). Association of rs10965219 with platelet reactivity persisted after adjustment for CAC, a measure of underlying atherosclerotic burden known to affect platelet reactivity. We then tested rs10965219 for association with platelet function in 2364 subjects from the Framingham Heart Study and 1169 subjects from the Genetic Study of Aspirin Responsiveness. The rs10965219 G allele (frequency 51% across all 3 populations) was significantly associated with higher platelet reactivity in the Framingham Heart Study (P=0.001) and trended toward higher reactivity in the Genetic Study of Aspirin Responsiveness (P=0.087); the combined P value for metaanalysis was 0.0002.

Conclusions—

These results suggest that risk alleles at 9p21.3 locus may have pleiotropic effects on myocardial infarction/coronary artery disease and stroke risk, possibly through their influence on platelet reactivity.

 
 
 
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