Genetic variability of platelet glycoprotein Ibα gene

Abstract

Platelet membrane glycoprotein (GP) Ibα is a critical component of platelet adhesion complex to subendothelium structures following tissue injury or pathological surfaces, such as atherosclerotic plaques. Polymorphisms of the GPIbα gene have been associated with a high risk for occlusive vascular disease, and its distribution varies considerably among distinct populations. These polymorphisms comprise the human platelet antigen (HPA)‐2 system, the −5C/T dimorphism of the Kozak sequence, and the variable number of tandem 39‐bp repeats (VNTR). Here we report the prevalence of the GPIbα gene polymorphisms among Brazilians, a highly ethnically diverse population. We analyzed 492 subjects of European, African, or Indigenous origin. It was possible to determine ten distinct haplotypes. The most common (∽40%) haplotype was the Kozak‐TT/HPA‐2aa/VNTR‐CC for both Caucasian and African descent. However, among Indigenous, Kozak‐TT/HPA‐2aa/VNTR‐CC and Kozak‐TC/HPA‐2aa/VNTR‐CC were equally present. Although a strong linkage disequilibrium between VNTR and HPA‐2 polymorphism had also been observed, here we determined incomplete linkage disequilibrium in 10% of subjects from all ethnic groups. VNTR‐E, a rare variant lacking the 39‐bp repeat, was identified in two unrelated subjects, and functional platelet studies revealed no abnormalities. The VNTR‐A allele, the largest variant containing four copies of the repeats, was not identified in this population. However, homozygosity for the VNTR‐A allele (Kozak‐TT/HPA‐2aa/VNTR‐AA) was determined in two distinct species of nonhuman primates. These results suggest a greater complex evolutionary mechanism in the macroglycoprotein region of the GPIbα gene and may be useful in the design of gene–disease association studies for vascular disease. Am. J. Hematol. 77:107–116, 2004. © 2004 Wiley‐Liss, Inc.

Platelet GPIbα, GPIV and vWF polymorphisms and fatal pre-hospital MI among middle-aged men

“…Congenital defects in the complex lead to bleeding disorders characterized by prolonged and excessive bleeding from mucosal membranes [20]. The C allele of the -5T/C Kozak sequence polymorphism of the GPIba on platelet surface affects directly to the levels of GP Ib-IX-V complex [9,21]. The effect might influence the risk of thrombosis, but the results published on the association of the Kozak polymorphism with CAD and MI have been conflicting [18,[22][23][24][25][26][27][28].…”

Gene Polymorphism of Platelet Glycoprotein I bα in Chinese Patients with Large- and Small-Artery Subtypes of Ischemic Stroke

“…One polymorphism is a certain C/T transition in the von Willebrand factor binding domain of GP Ι bα, resulting in an amino acid dimorphism (Thr/Met) at position 145 of GP Ι bα and may be influencing the function of GP Ι bα. This polymorphism is a known molecular basis of platelet alloantigen system, human platelet antigen 2 (HPA2; 2a/2b)[7,8,9]. …”