NH2-terminal globular domain of human platelet glycoprotein Ib alpha has a methionine 145/threonine145 amino acid polymorphism, which is associated with the HPA-2 (Ko) alloantigens.

Abstract

The glycoprotein (GP) Ib/IX complex, a prominent platelet GP complex, is the primary receptor for vWF. Previously, we have established that an antigenic polymorphism of platelets, the HPA-2 or Ko alloantigen system, is located on the 45-kD amino-terminal globular domain of GPIba. With the polymerase chain reaction, we have amplified two segments of the GPIba gene coding for the first 382 amino acids of two HPA-2a and two HPA-2b homozygous individuals. Nucleotide sequence analysis revealed as the only difference a C-T polymorphism at position 434 of the coding region for the mature protein. This base change results in a substitution of threonine (ACG) in HPA-2a (Ko") to methionine (ATG) in HPA-2b (Ko*) at amino acid position 145. The C-T polymorphism is reflected in a difference in restriction enzyme recognition, resulting in an Aha 2-site in the HPA-2b allele and a SfaN1 site in the HPA-2a allele. Restriction fragment length polymorphism analysis of the amplified DNA of 3 HPA-2(a-,b+), 2 HPA-2(a+,b+), and 11 HPA-2(a+,b-) donors showed that these restriction sites were associated with the HPA-2 alleles. DNA-typing for the HPA-2 alloantigen system on genomic DNA obtained from a small number of cells may be applied for determining the genotype of a fetus from an immunized mother or of severely thrombocytopenic patients. (J. Clin. Invest. 1992. 89:381-384.) Key

The human platelet alloantigens Br(a) and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin subunit alpha 2).

“…Platelet RNA PCR technology ( 14) has made it possible to assign single nucleotide substitutions to each of the currently recognized biallelic platelet alloantigen systems, pTA, Ko, Bak, and Pen (15)(16)(17)(18). Recently, the complete amino acid sequence of GPIa has been deduced from the nucleotide sequences of human lung fibroblast ( 19).…”

Platelet functional implications of glycoprotein Ibα polymorphisms in African Americans

“…The GP Iba gene is located on the short arm of chromosome 22 and has at least five polymorphic loci [2,4]. One of these loci is known as Ko and is responsible for the human platelet alloantigen system, human platelet antigen-2 (HPA-2) [5]. The Ko (also known as HPA-2 or Sib) polymorphism occurs when there is a G ?…”

“…The Ko (also known as HPA-2 or Sib) polymorphism occurs when there is a G ? A substitution at position 524 of the mRNA [5]. This substitution leads to a replacement of threonine by methionine at residue 145.…”

“…The Ko b HPA-2a is represented by a threonine at residue 145 and its allele frequency is 0.9 in a typical Caucasian population [5,9,10]. The presence of Ko a (HPA-2b) has been associated with an increased risk for the prevalence and severity of CAD [1].…”

StyI polymorphism at nucleotide 1610 in the human platelet glycoprotein Ib alpha gene

“…Extensive investigations have revealed the genetic abnormalities of the GPIb alpha gene, and some of them are responsible for the pathogenesis of Bernard-Soulier syndrome. Other mutations such as TaqI and Bsu36I polymorphisms (Petersen and Handin, 1992), methionineZ4~/threonine amino acid dimorphism (Murata et al, 1992;Kuijers et aL, 1992) and molecular weight polymorphism (Moroi et al, 1984) have also been reported. When analyzed the GPIb alpha gene of patients with Bernard-Soulier syndrome, we found a novel polymorphism in the GPIb alpha gene.…”