Polymorphisms in the platelet-specific collagen receptor GP6 are associated with risk of nonfatal myocardial infarction in Caucasians.
OBJECTIVE
Glycoprotein 6 (GP6) is a platelet-specific collagen receptor implicated in the thrombotic pathway to acute myocardial infarction (AMI), but a possible genetic relationship between GP6 and AMI is poorly understood. We tested for the genetic association between AMI and single nucleotide polymorphisms (SNPs) in 24 loci, including GP6.


RESULTS
We conducted a case-control study of AMI and GP6 in a community-based population (n = 652 cases, 625 controls). We also examined men and women separately and stratified the latter by use of hormone replacement therapy (HRT). Among both sexes, the strongest association was for a protective missense polymorphism (rs1163662) in the GP6 gene (OR = 0.70; Bonferroni-adjusted p < 0.05). SNPs in GP6 were also strongly associated with AMI among women who reported ever taking HRT, but not among women who never took HRT. Haplotype analyses were consistent with the single-SNP findings.


CONCLUSIONS
In this sample of white non-Hispanic men and women, several SNPs in GP6 were significantly related to risk of AMI. Development of pharmacologic therapy directed towards platelet activity and thrombosis may reduce the incidence of AMI among at-risk groups.
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
J R
JR
Shaffer
C M
CM
Kammerer
J
J
Dorn
R E
RE
Ferrell
L
L
Iacoviello
M
M
Trevisan
R P
RP
Donahue
D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D012307:Risk Factors; D013927:Thrombosis / Q000235:genetics*; D044465:White People
D005819:Genetic Markers; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI