Tj. Kunicki et al., HEREDITARY VARIATION IN PLATELET INTEGRIN ALPHA(2)BETA(1) DENSITY IS ASSOCIATED WITH 2 SILENT POLYMORPHISMS IN THE ALPHA(2) GENE CODING SEQUENCE, Blood, 89(6), 1997, pp. 1939-1943
The integrin alpha(2) beta(1) is a receptor for collagen that plays a
fundamental role in the adhesion of blood platelets to the extracellul
ar matrix. We previously reported that platelet alpha(2) beta(1) level
s among randomly selected individuals can vary up to '10-fold and that
this correlates with differences in adhesiveness to type-I or type-II
I collagens. We have now found two linked, allelic polymorphisms withi
n the coding sequence of the alpha(2) gene that correlate with recepto
r density, TTT/TTC at codon phe(224) and ACA/ACG at codon Thr(246). By
Southern blot hybridization of specific antisense DNA probes to segme
nts of genomic DNA that encompass each coding region, we have determin
ed 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 statist
ically significant correlation between the alleles TTT...ACA (codons 2
24...246) and high receptor density (n=30; P <.002), whereas the compl
imentary alleles TTC...ACG are associated with low receptor density. H
eterozygous individuals express intermediate levels of this receptor,
and familial studies confirm that these allelic polymorphisms are inhe
rited characteristics. These findings prove that the level of platelet
alpha(2) beta(1) is an inherited trait. The molecular basis for recep
tor density remains to be determined, but our findings establish that
these silent alleles within the coding sequence of the alpha(2) gene a
re linked to the genetic basis for variation in receptor density. (C)
1997 by The American Society of Hematology.