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(Circulation. 2001;104:1459.)
© 2001 American Heart Association, Inc.

Brief Rapid Communication

Novel Platelet Membrane Glycoprotein VI Dimorphism Is a Risk Factor for Myocardial Infarction

S. A. Croft, BSc; N. J. Samani, MD, FRCP; M. D. Teare, PhD; K. K. Hampton, MD, MRCP, MRCPath; R. P. Steeds, MA, MRCP; K. S. Channer, MD, FRCP; M. E. Daly, PhD

From the Division of Genomic Medicine, University of Sheffield, Sheffield, UK (S.A.C., M.D.T., K.K.H., M.E.D.); the Department of Cardiology, University of Leicester, Leicester, UK (N.J.S.); and the Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK (R.P.S., K.S.C.).

Correspondence to Dr M.E. Daly, Division of Genomic Medicine, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK. E-mail m.daly{at}sheffield.ac.uk

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).

Methods and 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 ß-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 ß-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.

Key Words: myocardial infarction • genetics • platelets

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