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 Previous Article | Table of Contents | Next Article 
Hereditary variation in platelet integrin alpha 2 beta 1 density is
associated with two silent polymorphisms in the alpha 2 gene coding
sequence
TJ Kunicki, M Kritzik, DS Annis and DJ Nugent
Department of Molecular and Experimental Medicine, Scripps Research
Institute, La Jolla, CA 92037, USA.
The integrin alpha 2 beta 1 is a receptor for collagen that plays a
fundamental role in the adhesion of blood platelets to the extracellular
matrix. We previously reported that platelet alpha 2 beta 1 levels among
randomly selected individuals can vary up to 10-fold and that this
correlates with differences in adhesiveness to type-I or type- III
collagens. We have now found two linked, allelic polymorphisms within the
coding sequence of the alpha 2 gene that correlate with receptor density,
TTT/TTC at codon Phe224 and ACA/ACG at codon Thr246. By Southern blot
hybridization of specific antisense DNA probes to segments of genomic DNA
that encompass each coding region, we have determined the gene frequencies
of each allele in a random donor population (n = 65) to be 0.585
(TTC...ACG) and 0.415 (TTT...ACA). There is a statistically significant
correlation between the alleles TTT...ACA (codons 224...246) and high
receptor density (n = 30; P < .002), whereas the complimentary alleles
TTC...ACG are associated with low receptor density. Heterozygous
individuals express intermediate levels of this receptor, and familial
studies confirm that these allelic polymorphisms are inherited
characteristics. These findings prove that the level of platelet alpha 2
beta 1 is an inherited trait. The molecular basis for receptor density
remains to be determined, but our findings establish that these silent
alleles within the coding sequence of the alpha 2 gene are linked to the
genetic basis for variation in receptor density.
Volume 89,
Issue 6,
pp. 1939-1943,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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