New single nucleotide polymorphisms associated with differences in platelets reactivity in patients with type 2 diabetes treated with acetylsalicylic acid: genome-wide association approach and pooled DNA strategy.
The objective of this study was to use genome-wide association approach and pooled DNA strategy to search for new genomic loci associated with inter-individual differences in platelet reactivity in the diabetic patients during acetylsalicylic acid (ASA) treatment. Study cohort consisted of 297 diabetic patients who had been taking ASA (75 mg daily) for at least 3 months. We tested association of single nucleotide polymorphisms (SNPs) genotyped using high density microarray platform with several platelet reactivity assays, followed by individual genotyping of most significant SNPs identified in the microarray genomic scan. The highest statistical significance (p value of 0.0001-0.008 in individual genotyping) was observed for SNP located within the regulatory G-protein signaling (RGS) 7 gene (rs2502448) using recessive genetic model. The diabetic patients on ASA treatment and homozygotes for its minor allele were characterized by increased odds ratio of at 3.45 (confidence interval: 1.82-6.53) for high on ASA platelet reactivity (i.e. impaired ASA response) when compared with homozygotes for wild-type allele. The genome-wide approach might provide an opportunity to identify novel candidate genes and pathways related to platelet activation in diabetic patients.
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, 26/28 Krakowskie Przedmiescie, 02-927 Warsaw, Poland. mpostula@wum.edu.pl
Marek
M
Postula
Piotr K
PK
Janicki
Marek
M
Rosiak
Agnieszka
A
Kaplon-Cieslicka
Ewa
E
Trzepla
Krzysztof J
KJ
Filipiak
Dariusz A
DA
Kosior
Andrzej
A
Czlonkowski
Grzegorz
G
Opolski
D000368:Aged; D000483:Alleles; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets; D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism
D010975:Platelet Aggregation Inhibitors; D020710:RGS Proteins; C492039:RGS7 protein, human; D004247:DNA; D001241:Aspirin