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Hereditary variation in platelet integrin alpha 2 beta 1 density is associated with two silent polymorphisms in the
T J Kunicki1, M Kritzik, D S Annis
1Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Blood
|March 15, 1997
Summary
Platelet integrin alpha 2 beta 1 levels, crucial for collagen adhesion, are inherited. Linked genetic variations in the alpha 2 gene influence receptor density, impacting platelet function.
Area of Science:
- Molecular Biology
- Hematology
- Genetics
Background:
- Integrin alpha 2 beta 1 is a key platelet receptor for collagen.
- Platelet integrin alpha 2 beta 1 levels exhibit significant inter-individual variation.
- This variation correlates with differences in platelet adhesiveness to collagen types I and III.
Purpose of the Study:
- To identify genetic factors influencing platelet integrin alpha 2 beta 1 receptor density.
- To investigate the correlation between specific alpha 2 gene polymorphisms and receptor levels.
- To determine if platelet integrin alpha 2 beta 1 density is an inherited trait.
Main Methods:
- Identified two linked, allelic polymorphisms in the alpha 2 gene coding sequence (Phe224 and Thr246 codons).
- Utilized Southern blot hybridization with antisense DNA probes to analyze genomic DNA.
- Determined allele frequencies in a random donor population (n=65).
Main Results:
- Found a statistically significant correlation between TTT...ACA alleles (codons 224...246) and high integrin alpha 2 beta 1 receptor density (P < .002).
- The complementary TTC...ACG alleles were associated with low receptor density.
- Familial studies confirmed the inheritance of these allelic polymorphisms.
Conclusions:
- Platelet integrin alpha 2 beta 1 receptor density is an inherited trait.
- Specific silent alleles within the alpha 2 gene coding sequence are linked to variations in receptor density.
- These genetic variations provide a molecular basis for differences in platelet collagen receptor levels.