GLYCOPROTEIN IA C807T polymorphism

The Coagulation and Molecular Immunodiagnostics Laboratory of ITxM Diagnostics is pleased to offer a genetic assay for the detection of Glycoprotein Ia C807T Polymorphism.

BACKGROUND

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.

METHODS

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.

 CLINICAL SIGNIFICANCE

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:

Ø       Children, young individuals or pre-menopausal women with arterial thrombosis

Ø       Any individual with arterial disease in the absence of atypical cardiovascular risk factors

SPECIMEN REQUIREMENTS

In order to assure the accuracy of our test results, the GPIa C807T polymorphism assay must be performed on whole blood.

1.   Blood must be collected in one (1) yellow  top tube (ACD).   DO NOT centrifuge the specimen and DO NOT separate plasma.

2.   Ship sample at room temperature.

3.   Specimen must be received within 72 hours of collection.

4.     We request that a completed Genetic Consent Form accompany the specimen.

TEST INFORMATION

This test was developed and its performance characteristics determined by ITxM Diagnostics.  It has not been cleared or approved by the U.S. Food and Drug Administration.  This test is used for clinical purposes and should not be regarded as investigational or for research use.  This laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high complexity clinical testing.

FOR FURTHER INFORMATION CONTACT  412-209-7270  OR  1-800-967-9672 

REFERENCES 

1. Bussel, JB, Kunicki, TJ, Michelson, AD.  Platelets: New understanding of platelet glycoproteins and their role in disease.  Hematology (Am. Soc Hematol Educ Program; 222-240, 2000.
2. Beer, JH, Pederiva, S, Poniggia, L.  Genetics of platelet receptor single-nucleotide polymorphisms: clinical implications in thrombosis.  Ann. Med. 32: 10-14, 2000.
3. Reiner, AP, Kumar, PN, Schwartz, SM, et. al., Genetic variants of platelet glycoprotein receptors and risk of stroke in young women.  Stroke 31: 1628-1633, 2000.
4. Golanski, J, Golanski, R, Chizynski, K, et. al.,  Platelet hyperreactivity after coronary artery bypass grafting: the possible relevance to glycoprotein polymorphisms.  A preliminary report.  Platelets 12: 241-247, 2001.
5. Casorelli, I, DeStefano, V, Leone, AM, et. al.  The C807T/G873A polymorphism in the platelet glycoprotein Ia gene and the risk of acute coronary syndrome in the Italian population.  Br. J. Haematol. 114: 150-154, 2001.