Novel platelet membrane glycoprotein VI dimorphism is a risk factor for myocardial infarction.
BACKGROUND
Glycoprotein (GP) VI plays a crucial role in platelet activation and aggregation. We investigated whether polymorphic variation at the GP VI locus confers an increased risk of myocardial infarction (MI).


RESULTS
Coding and 5' and 3' non-coding regions of the GP VI gene were analyzed by polymerase chain reaction and conformation sensitive gel electrophoresis in 21 healthy subjects. Ten dimorphisms, 5 of which predicted amino acid substitutions (T13254C, A19871G, A21908G, A22630T, C22644A), were identified. Two core haplotypes involving 7 dimorphisms (C10781A and G10873A and all those predicting amino acid substitutions) were apparent. The contribution of the T13254C dimorphism, which predicted the substitution of serine 219 by proline, to risk of MI was assessed in 525 patients with acute MI and 474 controls, all aged <75 years. The allelic odds ratio (OR) for MI associated with the 13254C allele was 1.16 (95% CI, 0.91 to 1.46; P=0.23). Compared with corresponding control subgroups, the 13254CC genotype was more common among cases who were female (OR, 4.52; 95% CI, 1.23 to 16.64; P=0.029), nonsmokers (OR, 2.50; 95% CI, 0.98 to 6.38; P=0.048), aged >/=60 years (OR, 6.48; 95% CI, 1.47 to 28.45; P=0.009) or carried the beta-fibrinogen -148T allele associated with increased fibrinogen levels (OR, 10.49; 95% CI, 1.32 to 83.42; P=0.02). In logistic regression analysis that took other cardiovascular risk factors into account, the interactions of GP VI genotype with age (P=0.005) and beta-fibrinogen genotype (P=0.035) remained significant.


CONCLUSIONS
The GP VI 13254CC genotype increases the risk of MI, particularly in older individuals, and the interaction of the GP VI 13254C allele with other candidate risk alleles may accentuate this risk.
Croft
S A
SA
Division of Genomic Medicine, University of Sheffield, Sheffield, UK.
Samani
N J
NJ
Teare
M D
MD
Hampton
K K
KK
Steeds
R P
RP
Channer
K S
KS
Daly
M E
ME
D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000235:genetics*; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017422:Sequence Analysis, DNA
D005819:Genetic Markers; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI