HEREDITARY VARIATION IN PLATELET INTEGRIN ALPHA(2)BETA(1) DENSITY IS ASSOCIATED WITH 2 SILENT POLYMORPHISMS IN THE ALPHA(2) GENE CODING SEQUENCE

Citation
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
Citations number
39
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
89
Issue
6
Year of publication
1997
Pages
1939 - 1943
Database
ISI
SICI code
0006-4971(1997)89:6<1939:HVIPIA>2.0.ZU;2-6
Abstract
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.