The effect of β2-glycoprotein i on the dextran sulfate and sulfatide activation of the contact system (Hageman factor system) in the blood coagulation

Schousboe, Inger; Rasmussen, M.S.

doi:10.1016/0020-711x(88)90065-1

Cited by 34 publications

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“…β 2 GPI has been implicated in a variety of physiological pathways, including blood coagulation, haemostasis and the production of anti‐phospholipid antibodies (APA). β 2 GPI inhibits the contact activation of the intrinsic pathway by binding to and neutralizing negatively charged macromolecules that might enter the blood stream and therefore diminishes inappropriate activation of the blood coagulation pathway [13–16]. In in vitro studies, β 2 GPI‐deficient plasma is unable to inhibit the contact activation of blood coagulation [17] and therefore raises the possibility that persons deficient in β 2 GPI may be more susceptible to thrombosis.…”

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confidence: 99%

A functional polymorphism at the transcriptional initiation site in β₂‐glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of β₂‐glycoprotein I

Mehdi¹,

Manzi²,

Desai³

et al. 2003

European Journal of Biochemistry

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Human b 2 -glycoprotein I (b 2 GPI), also known as apolipoprotein H, has been implicated in haemostasis and the production of anti-phospholipid antibodies. There is a wide range of interindividual variation in b 2 GPI plasma levels that is thought to be under genetic control, but its molecular basis remains unknown. To understand the genetic basis of b 2 GPI variation, we analyzed the 5¢ flanking region of the b 2 GPI gene for mutation detection by DHPLC and identified a point mutation at the transcriptional initiation site ()1CfiA) with a carrier frequency of 12.1%. The mutation was associated with significantly lower b 2 GPI plasma levels (P < 0.0001) and low occurrence of anti-phospholipid antibodies in lupus patients (4.8% antibody-positive group vs. 16.6% in the antibody-negative group; P ¼ 0.019).Northern blot analysis confirmed that the )1CfiA mutation was associated with lower mRNA levels and it reduced the reporter (luciferase) gene expression by twofold. Electrophoretic gel mobility shift assay (EMSA) revealed that the )1CfiA mutation disrupts the binding for crude hepatic nuclear extracts and purified TFIID. These results suggest that the substitution of C with A at the b 2 GPI transcriptional initiation site is a causative mutation that affects its gene expression at the transcriptional level and ultimately b 2 GPI plasma levels and the occurrence of anti-phospholipid antibodies.Keywords: b 2 -glycoprotein I; apolipoprotein H; anti-phospholipid antibodies; polymorphism; lupus.Human b 2 -glycoprotein I (b 2 GPI), also known as apolipoprotein H, is a plasma glycoprotein of approximately 50 kDa [1], which is primarily expressed in liver and is associated with very low-density lipoproteins, high-density lipoproteins, and chylomicrons and it also exists in lipid-free form in plasma [2,3]. The gene organization of b 2 GPI has been characterized, which consists of eight exons, spanning 18 kb on chromosome 17q23-24 [4]. b 2 GPI is a single chain polypeptide of 326 amino acids [5][6][7][8] that shows extensive internal homology within its five consecutive homologous segments of approximately 60 amino acid each. These segments are referred to variously as GP-I domains [9], sushi domains [10], short consensus repeats (SCR) or complement control protein (CCP) repeats [5,11,12].b 2 GPI has been implicated in a variety of physiological pathways, including blood coagulation, haemostasis and the production of anti-phospholipid antibodies (APA). b 2 GPI inhibits the contact activation of the intrinsic pathway by binding to and neutralizing negatively charged macromolecules that might enter the blood stream and therefore diminishes inappropriate activation of the blood coagulation pathway [13][14][15][16]. In in vitro studies, b 2 GPIdeficient plasma is unable to inhibit the contact activation of blood coagulation [17] and therefore raises the possibility that persons deficient in b 2 GPI may be more susceptible to thrombosis. However, the role of b 2 GPIdeficiency in thrombosis is controversial [18][19][20]. Recently...

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A functional polymorphism at the transcriptional initiation site in β₂‐glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of β₂‐glycoprotein I

Mehdi¹,

Manzi²,

Desai³

et al. 2003

European Journal of Biochemistry

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“…It has a molecular mass of approximately 50 kDa and has been shown to consist of 326 amino acids with five attached glucosaminecontaining oligosaccharides.2 Several forms have been found and genetic studies indicate that three allelic variants are coded at a single gene IOCUS.~ Its physiological role is not known but it has been identified as a constituent of chylomicrons, and very-low-density and high-density lipoprotein^,^ and it is sometimes called Apolipoprotein H. 3 It is known that it can activate lipoprotein l i p a~e ,~ and that it inhibits the contact activation system in blood coagulation. 6 In the course of searching for potential new markers of renal tubular disorders, using a sensitive immunodot procedure, we discovered that &glycoprotein I could be readily detected in the urine of patients with tubular defects.…”

Section: Additional Key Phrases: Apolipoprotein-h; Renal Tubular Disomentioning

confidence: 99%

A Sandwich Enzyme-Linked Immunosorbent Assay for β₂-Glycoprotein I

et al. 1991

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SUMMARY.A solid-phase sandwich enzyme-linked immunosorbent assay for determining 0,-glycoprotein I in urine has been developed. It has a working concentration range of 5-40 pg/L and a detection limit of approximately 1 . 4 pg/L. The withinplate coefficient of variation (CV) falls between 1.4% and 2 -1 % , and the betweenbatch CV ranges from 5.2 to 6.0%. Recovery of P,-glycoprotein I added to urine varies between 96 and 110%. The assay can also be used for determining P,-glycoprotein I in serum. Additional key phrases: Apolipoprotein-H; renal tubular disordersBeta-2-glycoprotein I was identified in the perchloric acid soluble fraction of human plasma in 1961.' It has a molecular mass of approximately 50 kDa and has been shown to consist of 326 amino acids with five attached glucosaminecontaining oligosaccharides.2 Several forms have been found and genetic studies indicate that three allelic variants are coded at a single gene IOCUS.~

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“…ApoH binds to platelets, mitochondria, heparin, DNA, dextran sulfate, anionic phospholipids, hepatitis B virus (HBV), human immunodeficiency virus (HIV), and calmodulin (Kroll et al 1976;Kostner 1979a, 1979b;Schousboe 1979Schousboe , 1980Schousboe , 1985Schousboe , 1988Polz et al 1980;Wurm 1984;Arvieux et al 1994;Schousboe and Rasmussen 1988;Mehdi et al 1994Mehdi et al , 1996Rojkjaer et al 1997;Klaerke et al 1997;Stefas et al 1997). ApoH also inhibits the contact activation of blood coagulation (Schousboe 1985), activates lipoprotein lipase (Nakaya et al 1980), adheres to activated platelets (Schousboe 1980), and inhibits prothrombinase activity (Nimpf et al 1986).…”

Section: Introductionmentioning

confidence: 96%

Genetic variation in the apolipoprotein H (β2-glycoprotein I) gene affects plasma apolipoprotein H concentrations

et al. 1999

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Apolipoprotein H (apoH, protein; APOH, gene) is a single chain glycoprotein that exists in plasma both in a free form and in combination with lipoprotein particles. ApoH has been implicated in several physiologic pathways, including lipid metabolism, coagulation, and the production of antiphospholipid antibodies. The wide range of interindividual variation in plasma apoH levels is thought to be under genetic control, but its molecular basis is unknown. APOH displays a common structural polymorphism with the occurrence of three common alleles (APOH*1, APOH*2, and APOH*3), the APOH*2 allele being the most frequent in all populations. The relationship between the APOH polymorphism and plasma apoH levels is unknown. In this study, we have determined the impact of this APOH polymorphism on apoH levels in 455 normoglycemic non-Hispanic Whites (220 men and 235 women) from the San Luis Valley, Colorado. Mean plasma apoH levels, determined by capture enzyme-linked immunosorbent assay, were 20.0 +/- 0.2 mg/dl (range: 3.4-31.2 mg/dl) with no significant difference between men and women. In women, but not in men, age had a significant effect on plasma apoH levels explaining 3.4% of its phenotypic variance. ApoH levels also correlated positively with cholesterol (P = 0.015), HDL-cholesterol (P = 0.044), and triglyceride (P = 0.037) in women, but not in men. An analysis of variance (ANOVA) of adjusted plasma apoH levels showed significant association with the APOH polymorphism in both men and women (P < 0.0001), and the APOH polymorphism accounted for 11.4% and 13.6% of the variation in apoH levels in men and women, respectively. Compared with the APOH*1 and APOH*2 alleles, the APOH*3 allele was associated with significantly lower plasma apoH levels. At the molecular level, APOH*3 can be further subdivided into two distinct forms, called APOH*3W and APOH*3B. The APOH*3W form is more common in US Whites and is the result of a missense mutation at codon 316. An ANOVA for the codon 316 polymorphism revealed that this polymorphism is a major determinant of plasma apoH variation (P < 0.0001). This study indicates that common genetic variation in the APOH gene is a significant determinant of plasma apoH levels in non-Hispanics Whites and should be useful in evaluating the role of the APOH genetic variation in various metabolic pathways in which apoH has been implicated.

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The effect of β2-glycoprotein i on the dextran sulfate and sulfatide activation of the contact system (Hageman factor system) in the blood coagulation

Cited by 34 publications

References 19 publications

A functional polymorphism at the transcriptional initiation site in β₂‐glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of β₂‐glycoprotein I

A functional polymorphism at the transcriptional initiation site in β₂‐glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of β₂‐glycoprotein I

A Sandwich Enzyme-Linked Immunosorbent Assay for β₂-Glycoprotein I

Genetic variation in the apolipoprotein H (β2-glycoprotein I) gene affects plasma apolipoprotein H concentrations

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The effect of β2-glycoprotein i on the dextran sulfate and sulfatide activation of the contact system (Hageman factor system) in the blood coagulation

Cited by 34 publications

References 19 publications

A functional polymorphism at the transcriptional initiation site in β2‐glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of β2‐glycoprotein I

A functional polymorphism at the transcriptional initiation site in β2‐glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of β2‐glycoprotein I

A Sandwich Enzyme-Linked Immunosorbent Assay for β2-Glycoprotein I

Genetic variation in the apolipoprotein H (β2-glycoprotein I) gene affects plasma apolipoprotein H concentrations

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Resources

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A functional polymorphism at the transcriptional initiation site in β₂‐glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of β₂‐glycoprotein I

A functional polymorphism at the transcriptional initiation site in β₂‐glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of β₂‐glycoprotein I

A Sandwich Enzyme-Linked Immunosorbent Assay for β₂-Glycoprotein I