Genetic Variants of Coagulation Factors

Vitamin K-dependent (anti)coagulation factors (factor II, VII, IX, X protein C and S) undergo a conformational transition upon binding of Ca(II), which is a prerequisite for their normal function. Abnormalities in these properties occur during vitamin K deficiency or treatment with anti vitamin K drugs and in some genetic variants of coagulation factors. Immunological assays utilizing antibodies against the Ca(II)-stabilized structure are useful to detect such abnormalities.Starting from specific rabbit antisera antibody populations specific for the Ca(II)-dependent conformation of factor II, VII, IX, X and protein C and S were isolated using immuno-affinity procedures. Subsequently immunoradiometric assays specific for the Ca(II)-dependent (Ca(II)Ag) and Ca(II)-independent (NonCa(II)Ag) conformations of the different proteins were developed. These assays were used for the analysis of plasmas of patients stably treated with oral anticoagulants; Ca(II)Ag, NonCa(II)Ag and their ratio were measured as function of the intensity of the treatment (INR 2.4 to 4.8). The same parameters were measured in plasmas of patients with hereditary coagulation disorders. After treatment with oral anticoagulation with an antivitamin K drug reduced ratios of Ca(II)Ag/-NonCa(II)Ag were observed for factor II, VII, IX, protein C and protein S. However, the actual degree of reduction and its dependence on the intensity of treatment varied for the different vitamin K-dependent proteins. In general Ca(II)Ag levels correspond nicely with the procoagulant activity of the concerning proteins. These data provide indirect evidence for the existence of abnormal (non and/or subcarboxylated) forms of the vitamin K-dependent proteins during oral anticoagulant treatment.Genetic variants with a mutation in one of the sites involved in the formation of the Ca(II)-s tab i1ized structure could be detected for factor IX, factor VII and factor II. However, the extent of reduction of the ratio Ca(II)Ag/-NonCa(II)Ag differed considerably in those variants.

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Visualization of the Platelet-Plasma Interface

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100079905 ◽

1977 ◽

Vol 35 ◽

pp. 494-495

Author(s):

D. C. Brindley ◽

M. McGill

Keyword(s):

Platelet Rich Plasma ◽

Coagulation Factors ◽

Platelet Membrane ◽

Rabbit Platelet ◽

Surface Coat ◽

Special Relationship ◽

Routine Method ◽

Embedding Technique ◽

Biochemical Analyses ◽

Adsorptive Properties

Morphological and cytochemical studies of platelets have reported a surface coat, or glycocalyx, external to the plasma membrane (1). Biochemical analyses have likewise confirmed the highly adsorptive properties of platelets as transporters of coagulation factors (2). However, visualization of the platelet membrane by conventional EM procedures does not reflect this special relationship between the platelet and its plasma environment. By the routine method of alcohol-propylene oxide dehydration for Epon embedding, the lipid bilayer nature of the platelet membrane appears similar to other blood cells (Fig. 1). A new rapid embedding technique using dimethoxypropane (DMP) as dehydrating agent (13) has permitted ultrastructural analyses of the surface features of the platelet-plasma interface.Aliquots of human or rabbit platelet-rich plasma (PRP) were added to equal volumes of 6% glutaraldehyde in Millonig's buffer at 37° for 45 minutes, rinsed in buffer and postfixed in 1% osmium in Millonig's buffer for 45 minutes.

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Genetic Variants Confer Susceptibility to JIA, Type 1 Diabetes, and Celiac Disease

Internal Medicine News ◽

10.1016/s1097-8690(11)70096-8 ◽

2011 ◽

Vol 44 (2) ◽

pp. 50

Author(s):

MICHELE G. SULLIVAN

Keyword(s):

Type 1 Diabetes ◽

Celiac Disease ◽

Genetic Variants

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Genetic Variation: Impact on Folate (and Choline) Bioefficacy

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000040 ◽

2010 ◽

Vol 80 (45) ◽

pp. 319-329 ◽

Cited By ~ 9

Author(s):

Allyson A. West ◽

Marie A. Caudill

Keyword(s):

Carbon Metabolism ◽

Genetic Variants ◽

Plasma Homocysteine ◽

Water Soluble ◽

Gene Interactions ◽

Dietary Folate ◽

Methyl Donors ◽

Common Genetic Variants ◽

One Carbon Metabolism ◽

The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

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