Maximum likelihood approach suggests positive selection in platelet integrin αIIbß3 in mammalian species.

Platelet integrin αIIbß3 is crucial for platelet aggregation. Although structural and functional characteristics of this protein have been extensively studied, the evolutionary pattern studies of this protein complex in mammals are scarce. Here, we addressed this question using maximum likelihood approaches to identify codons that are evolving under positive selection. Likelihood of positive selection was estimated using CODEML implemented in PAML software applied to integrin αIIbß3 derived from nucleotide sequences of 10 different mammalian species. Four codons in mature αIIb-subunit (corresponding to residues 150, 184, 193, and 370) and three codons in mature ß3-subunit (corresponding to residues 129, 440, and 444) showed signs of positive selection with posterior probabilities over 95%. The different amino acids observed for each of the positively selected residues detected showed different physicochemical properties. These results open new research avenues to understand the physiological importance of specific residues and should allow for a better understanding of the function and the different interactions of each residue within the mature protein.

Influence of genetic variations in platelet glycoproteins and eNOS in the development of arterial ischaemia of lower limbs in type 2 diabetes mellitus patients.

Endothelial and platelet dysfunction increase the atherothrombotic risk in diabetes mellitus patients. Therefore, arterial ischaemia of lower limbs is an important complication in diabetes mellitus. In the present work, type 2 diabetic patients were classified by a podiatrist into presence or absence of arterial ischaemia of lower limbs. Several polymorphisms in platelet glycoproteins and eNOS genes were evaluated. Our results suggest that the -5CC genotype in Kozak sequence of GPIbα may be associated with a higher risk of developing arterial ischaemia of lower limbs in type 2 diabetes mellitus patients.

Allelic and genotypic frequencies of platelet glycoprotein polymorphisms in a Portuguese population.

INTRODUCTION AND OBJECTIVES: We studied genotypic and allelic frequencies of polymorphisms that can affect platelet function, namely the Kozak, VNTR and HPA-2 polymorphisms of glycoprotein Ibα, the Pl(A) polymorphism of glycoprotein IIIa and the C807T polymorphism of glycoprotein Ia, in a Portuguese population composed of 227 donors. METHODS: PCR-RFLP was used to assess the Kozak, HPA-2, Pl(A) and C807T polymorphisms. The VNTR polymorphism was discriminated by different weight bands on electrophoresis. RESULTS: All genotypic frequencies were in Hardy-Weinberg equilibrium and do not differ from other Caucasian populations. Genotypic frequencies were 68.3%, 26.9% and 4.8% for Pl(A1/A1), Pl(A1/A2) and Pl(A2/A2) genotypes of the Pl(A) polymorphism, 79.3%, 20.3% and 0.4% for TT, TC and CC genotypes of the Kozak polymorphism, 81.1%, 18.9% and 0.0% for aa, ab and bb genotypes of the HPA-2 polymorphism, 15.4%, 0.9%, 70.5%, 11.5%, 1.3% and 0.4% for BC, BD, CC, CD, DD and CE genotypes of the VNTR polymorphism, and 39.7%, 50.2% and 10.1% for CC, CT and TT genotypes of the C807T polymorphism. CONCLUSIONS: The Portuguese population has now been characterized in terms of major platelet glycoprotein polymorphisms, which will be an important tool for further studies to assess the role of platelet glycoproteins in individual predisposition to prothrombotic conditions and response to antithrombotic therapy.