Blood, Vol. 94 No. 11 (December 1), 1999:
pp. 3959-3960
CORRESPONDENCE
Prothrombotic Genetic Risk Factors and Myocardial Infarction at
Young Age
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LETTER |
To the Editor:
We have read with interest the report by Ardissino et
al,1 which concludes that the presence of the
PlA2 polymorphic allele is the only prothrombotic genetic
factor associated with the risk of myocardial infarction at a
young age. These authors find a significant interaction between the
presence of the PlA2 allele and smoking.
We studied 178 men younger than 50 years old who were
diagnosed with coronary disease.2 The prevalence
of PlA2 allele was 24% in case subjects compared with 26%
in 200 age- and sex-matched control subjects. We also investigated
whether the PlA2 allele was associated with other risk
factors. No differences were found in patients between
smokers (40 of 167) and nonsmokers (3 of 11) (24% v
27%), hypertensives (18 of 66) and normotensives (25 of 112)
(27% v 22%), diabetics (4 of 15) and nondiabetics (39 of 163) (27% v 24%), and neither when the total
cholesterol/high-density lipoprotein [HDL] cholesterol ratio greater
than (37 of 150) or less than 5 (5 of 28) was used (25% v
18%). In reference to the biochemical parameters,3 the
only significant difference was found for LDL-cholesterol
values. Thus, average low-density lipoprotein (LDL)-cholesterol values
were 167 ± 75 mg/dL among PlA2-carrier patients and 146 ± 36 mg/dL
among PlA1/PlA1 patients (P < .02).
Weiss et al4 described a high frequency of family
members homozygous for Pro at codon 33 (the PlA2 allele) in kindreds with a high prevalence of acute coronary events at a young age (<60
years). This observation led them to postulate that carriers of the
PlA2 allele could be more susceptible to develop symptomatic coronary
heart disease. In a case-control study,5 the same authors
found a higher prevalence of the PlA2 allele among patients than among
controls, and the association was strongest in patients who had
coronary events before the age of 60 years.
At least 2 case-control studies6,7 failed to find
the same association between the PlA2 allele of the glycoprotein IIIa gene and acute coronary thrombosis. In agreement with these, we didn't
find a significant difference between genotypic frequencies of
patients and controls.
The discrepancies may reflect differences in the definition of
the phenotype in the patients or in the selection and size of both
cases and controls. We analyzed patients and controls from a
homogeneous Caucasian population. Our study was based on a number of
patients (178 cases) and controls (200 individuals) high enough to
define any statistically significant association.
In addition, we did not find a significantly increased
frequency of the PlA2 allele among patients younger than 50 years. Finally, A2A2 homozygous patients were not more frequent among patients
than among controls, and did not develop coronary disease at a younger
age. Taken together, these data suggest a true lack of association
between the PlA2-allele and the development of acute coronary
artery disease in our population.
Coronary artery disease is a polygenic trait in which
inherited and environmental factors interact to drive the
disease process. Some gene polymorphisms could be associated
to the disease in some populations and not in others. Thus,
it is possible that in those populations showing an
association between PlA2 and coronary disease, this allele is in
linkage disequilibrium with some other mutation at the Pl gene, this
mutation being responsible for the association. We are currently
searching for mutations at the glycoprotein IIIa gene (single-strand
conformation polymorphism analysis) in our patients.
We investigated whether the PlA2 allele is associated with
other risk factors. We found no evidence of association between the
PlA2 allele and smoking status, hypertension, or diabetes. These data
are in agreement with the work of Ridker et al.7 In
addition, the association between PlA2 and dyslipemia was also investigated. We found that patients with the PlA2 allele showed a
significantly higher concentration of LDL cholesterol.
Finally, we agree with the authors that prospective studies
are needed to evaluate the clinical value of the interaction between environmental and genetic factors.
Alberto Batalla
Department of Cardiology Cabueñes
Hospital
Gijón, Spain
Julián R. Reguero
Gustavo I. Cubero
E. Coto
Department of Cardiology and
Laboratory of Molecular Genetics
Central Hospital of Asturias
Oviedo, Spain
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REFERENCES |
1.
Ardissino D, Mannucci PM, Merlini PA, Duca F, Fetiveau R, Tagliabue L, Tubaro M, Galvani M, Ottani F, Ferrario M, Corral J, Margaglione M:
Prothrombotic genetic risk factors in young survivors of myocardial infarction.
Blood
94:46, 1999[Abstract/Free Full Text]
2.
Batalla A, Reguero JJR, Cubero GI, Molina BD, Braga S, Menéndes MJ, Coto E:
Polymorphisms of the platelet receptor IIIa in early coronary disease.
J Am Coll Cardiol
31:76a, 1998 (abstr)
3.
Batalla A, Reguero JJR, Cubero GI, Molina BD, Braga S, Hevia S, Menéndez MJ, Coto E, Cortina A:
Polymorphisms of the platelet receptor IIIa and lipid levels in early coronary disease.
Atherosclerosis
134:65a, 1997 (abstr)
4.
Weiss EJ, Goldschidit-Clermont PJ, Grygoryev D, Jin Y, Kickler TS, Bray PF:
A monoclonal antibody (SZ21) specific platelet GPIIIa distinguishes PlA1 and PlA2.
Tissue Antigens
46:374, 1995[Medline]
[Order article via Infotrieve]
5.
Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler TS, Becker LC, Weiss JL, Gerstenblith G, Goldschidit-Clermont PJ:
A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis.
N Engl J Med
334:1090, 1996[Abstract/Free Full Text]
6.
Marian AJ, Brugada R, Kleiman NS:
Platelet glycoprotein IIIa PlA polymorphism and myocardial infarction.
N Engl J Med
334:1071, 1996[Free Full Text] (letter)
7.
Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K:
Pl A1/A2 polymorphism of platelet glycoprotein IIIa and risk of myocardial infarction, stroke and venous thrombosis.
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[Order article via Infotrieve]
