Localization of the Br Polymorphism on a 144 bp Exon of the GPIa Gene and Its Application in Platelet DNA Typing

Kalb, R; Santoso, Sentot; Unkelbach, K.; Kiefel, V.; Mueller‐Eckhardt, C.

doi:10.1055/s-0038-1642498

Cited by 69 publications

(35 citation statements)

References 10 publications

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“…Consequently, although the reported associations for ITGA2 C807T (rs1126643), 22 GP1BA T-5C, 27,31 and the GP6 haplotype b 23 have been replicated, others have not been as reproducible. 32,33 Genes for the following proteins and their representative SNPs have been included in various gene association studies to assess variation in platelet function among normal persons ( 36,37 C-52T, 38 and G1648A) 39 ; 8. Integrin subunit ␣IIb (platelet GPIIb) (ITGA2B I843S) 40 ; 9.…”

Section: Candidate Gene Association Studiesmentioning

confidence: 99%

The genetics of normal platelet reactivity

Kunicki

Nugent

2010

Blood

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Genetic and environmental factors contribute to a substantial variation in platelet function seen among normal persons. Candidate gene association studies represent a valiant effort to define the genetic component in an era where genetic tools were limited, but the single nucleotide polymorphisms identified in those studies need to be validated by more objective, comprehensive approaches, such as genome-wide association studies (GWASs) of quantitative functional traits in much larger cohorts of more carefully selected normal subjects. During the past year, platelet count and mean platelet volume, which indirectly affect platelet function, were the subjects of GWAS. IntroductionInterindividual platelet responsiveness to a variety of agonists is highly variable, as documented in several studies of large cohorts of normal persons. [1][2][3][4][5][6][7][8][9][10][11][12] At the same time, these and other studies of siblings, twins, and families with a history of coronary artery disease (CAD) have documented that intraindividual responsiveness is highly reproducible over time, regardless of the agonist tested or the chosen method of assessment. These findings strongly suggest that there is a high level of heritability of platelet function, and this has prompted numerous attempts to define the genetic basis for platelet function variability. A summary of platelet functionTo fully appreciate the gene association studies, it is necessary to briefly summarize key aspects of platelet function and establish a molecular and physiologic basis for the selection of genes to study.When a blood vessel is damaged, circulating platelets interact with components of the extracellular matrix, particularly collagen, and a complex series of receptor-ligand interactions ensues that ultimately leads to the formation of a stable platelet plug or thrombus. This process is a continuum of at least 3 phases that we can describe as initiation, extension, and consolidation, each of which entails the cooperation of a different group of receptors.In the initiation phase, plasma von Willebrand factor (VWF) binds to collagen via its A3 domain and becomes structurally altered such that its A1 domain then binds to the platelet membrane receptor glycoprotein Ib-IX-V complex (GPIb complex). It is the GPIb␣ or larger subunit of GPIb that makes direct contact with VWF. This association is a requisite step in the adhesion of platelets to exposed thrombogenic surfaces at sites of vessel wall injury or in regions of atherosclerotic plaque rupture. Concurrently, a more stable platelet monolayer is formed on the collagen surface mediated predominantly by the platelet-specific receptor glycoprotein VI (GPVI) and platelet integrin ␣ 2 ␤ 1 .The engagement of these receptors enhances platelet activation leading to the extension phase, mediated largely by the conversion of prothrombin to thrombin at the activated platelet surface and the secretion of active compounds from platelet granules (␣-granules and ␦-granules), which can further stimulate platelets. One of...

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Section: Candidate Gene Association Studiesmentioning

confidence: 99%

The genetics of normal platelet reactivity

Kunicki

Nugent

2010

Blood

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“…HPA-1 and HPA-3 were genotyped using PCR sequence-specifi c primers according to Kluter et al (21) , and the CRP gene was used as the internal positive control in all reactions. HPA-5 was genotyped using PCRrestriction fragment length polymorphism analysis according to Kalb et al (22) . A negative control was used in all of the PCR assays.…”

Section: Deoxyribonucleic Acid Extraction and Human Platelet Antigen mentioning

confidence: 99%

The absence of the human platelet antigen polymorphism effect on fibrosis progression in human immunodeficiency virus-1/hepatitis C virus coinfected patients

Picelli

Tanikawa

Grotto

et al. 2015

Rev. Soc. Bras. Med. Trop.

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“…We studied 2 nucleotide polymorphisms located at 807C/T bp and 1648A/G bp within the coding region of the ␣ 2 gene 25,26 and single-base substitutions at 2 positions, Ϫ92C/G and Ϫ52C/T, within the proximal 5Ј-regulatory region of the ␣ 2 gene. 13 Genotyping of these 4 polymorphisms was conducted using an adapted method of DNA amplification by polymerase chain reaction (PCR) procedure with specific primers.…”

Section: Dna Genotypingmentioning

confidence: 99%

Association of the −92C/G and 807C/T Polymorphisms of the α ₂ Subunit Gene With Human Platelets α ₂ β ₁ Receptor Density

Ajzenberg

Berroëta

Philip

et al. 2005

ATVB

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Objective-Platelet adhesion to the subendothelial tissue via the collagen receptor ␣ 2 ␤ 1 is a crucial event in vascular biology. Although evidence has been provided that the number of platelets ␣ 2 ␤ 1 copies is genetically determined, the molecular change primary responsible has not been yet elucidated. The aim of our present study was to investigate the effect of combined polymorphisms within both regulatory (Ϫ52C/T and Ϫ92C/G) and coding regions (807C/T and 1648A/G) of the ␣ 2 subunit gene on human platelets ␣ 2 ␤ 1 receptor density and/or susceptibility to coronary artery disease (CAD). Methods and Results-Among 254 cardiac surgery patients, no evidence was found for an association between the ␣ 2 subunit gene polymorphisms and CAD. In contrast, in a subgroup of 113 patients, we observed a significant association between all polymorphisms except Ϫ52C/T and ␣ 2 ␤ 1 receptor level. Furthermore, when 3 groups of patients were defined according to the tertiles of platelets ␣ 2 ␤ 1 copies, the Ϫ92C/807T haplotype was more frequent in the group of patients with high ␣ 2 ␤ 1 receptor level. Key Words: Ϫ92C/G Ⅲ 807C/T polymorphism Ⅲ ␣ 2 ␤ 1 density V essel wall injury triggers platelet activation and platelet plug formation, followed by the formation of fibrincontaining thrombi that occlude the site of injury. The interaction of platelet receptors with subendothelial components such as collagen is central to these events, which both limit blood loss at sites of tissue trauma but may also obstruct diseased vessels, leading to ischemia and infarction of vital organs. The direct platelet-collagen interaction is mediated by Ն2 receptors, the integrin ␣ 2 ␤ 1 and the nonintegrin receptor glycoprotein VI (GPVI), although there are likely to be others. 1 It is now considered that GPVI provides the primary collagen signal that activates and recruits the integrin receptor ␣ 2 ␤ 1 to further amplify collagen signals and fully activate platelets through a common intracellular signaling pathway. 2 Conclusion-These

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Localization of the Br Polymorphism on a 144 bp Exon of the GPIa Gene and Its Application in Platelet DNA Typing

Cited by 69 publications

References 10 publications

The genetics of normal platelet reactivity

The genetics of normal platelet reactivity

The absence of the human platelet antigen polymorphism effect on fibrosis progression in human immunodeficiency virus-1/hepatitis C virus coinfected patients

Association of the −92C/G and 807C/T Polymorphisms of the α ₂ Subunit Gene With Human Platelets α ₂ β ₁ Receptor Density

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Localization of the Br Polymorphism on a 144 bp Exon of the GPIa Gene and Its Application in Platelet DNA Typing

Cited by 69 publications

References 10 publications

The genetics of normal platelet reactivity

The genetics of normal platelet reactivity

The absence of the human platelet antigen polymorphism effect on fibrosis progression in human immunodeficiency virus-1/hepatitis C virus coinfected patients

Association of the −92C/G and 807C/T Polymorphisms of the α 2 Subunit Gene With Human Platelets α 2 β 1 Receptor Density

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Association of the −92C/G and 807C/T Polymorphisms of the α ₂ Subunit Gene With Human Platelets α ₂ β ₁ Receptor Density