The GPIa/IIa complex mediates platelet adhesion to collagen. Although the GPIa C807T polymorphism does not change the amino acid sequence, it has been associated with the difference in the GPIa/IIa receptor levels on the platelet surface. Carriers of the 807T allele express higher levels of GPIa/IIa, while carriers of the 807C allele exhibit lower expression of the integrin. This polymorphism has been implicated to be associated with an increased risk of arterial thrombosis. Additional studies suggest this is a mild risk factor and is particularly important in synergism with known risk factors such as smoking, hypertension, diabetes or proteinuria, which may enhance its contribution to the overall cardiovascular risk.
Lymphocytes are processed to extract DNA. Third Wave Technologies’ Invader assay is used to genotype the target DNA. Briefly, two specific oligonucleotide probes and controls hybridize in tandem to a specific region of the gene encoding the mutation site. Cleavase III enzyme cleaves at a specific invasive structure generated within the probe oligonucleotides creating products. These sequential cleavage reactions produce 1-10 million fluorescein labeled products per target sequence hour. This results in the accumulation of a signal molecule only when the specific target DNA or control sequence is present. A fluorescent multiwell plate reader is used to quantitate signal amplification for interpretation of genotype. Homozygosity for the C807T allele (T/T) is associated with increased arterial thrombotic risk.
Platelets play an important part in arterial thrombosis therefore it is important to consider the role adhesion molecules of the platelet surface play in increasing arterial risk. Glycoprotein Ia/IIa is the major platelet collagen receptor and is responsible for platelet adherence to exposed vascular subendothelium. The single nucleotide polymorphism C807T allele is associated with increased collagen receptor levels and increased collagen induced platelet adhesion. Preliminary results suggest that the C807T variant of glycoprotein Ia may be a genetic risk factor for early-onset arterial thrombotic disease.
In general, screening for arterial thrombosis is best accomplished by evaluating for the traditional cardiovascular markers, such as diabetes mellitus, smoking, hypertension, and hypertriglyceridemia. The use of the glycoprotein Ia C807T assay may be of value in the following situations:
- Children, young individuals or pre-menopausal women with arterial thrombosis
- Any individual with arterial disease in the absence of atypical cardiovascular risk factors
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