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Evaluation of the r...
Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease
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- Zöller, Bengt (författare)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups
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- Garcia de Frutos, P. (författare)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups
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- Dahlbäck, Björn (författare)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups
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(creator_code:org_t)
- 1995
- 1995
- Engelska 8 s.
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Ingår i: Blood. - 0006-4971. ; 85:12, s. 3524-3531
- Relaterad länk:
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https://lup.lub.lu.s...
Abstract
Ämnesord
Stäng
- Type III protein S deficiency is characterized by a low plasma level of free protein S, whereas the total concentration of protein S is normal. In contrast, both free and total protein S levels are low in type I deficiency. To elucidate the molecular mechanism behind the selective deficiency of free protein S in type III deficiency, the relationship between the plasma concentrations of β-chain containing isoforms of C4b-binding protein (C4BPβ+) and different forms of protein S (free, bound, and total) was evaluated in 327 members of 18 protein S-deficient families. In normal relatives (n = 190), protein S correlated well with C4BPβ+ with free protein S (96 ± 23 nmol/L) being equal to the molar excess of protein S (355 ± 65 nmol/L) over C4BPβ+ (275 ± 47 nmol/L). In protein S-deficient family members (n = 117), the equimolar relationship between protein S (215 ± 50 nmol/L) and C4BPβ+ (228 ± 51 nmol/L), together with the high affinity of the interaction, resulted in low levels of free protein S (16 ± 10 nmol/L). Free protein S levels were distinctly low in proteinS-deficient members, whereas in 47 of the protein S-deficient individuals, the concentration of total protein S was within the normal range, which fulfills the criteria for type III deficiency. The remaining 70 had low levels of both total and free protein S and, accordingly, would be type I deficient. Coexistence of type I and type III deficiency was found in 14 families, suggesting the two types of protein S deficiency to be phenotypic variants of the same genetic disease. Interestingly, not only protein S but also C4BPβ+ levels were decreased in orally anticoagulated controls and even more so in anticoagulated protein S- deficient members, suggesting that the concentration of C4BPβ+ is influenced by that of protein S. In conclusion, our results indicate that type I and type III deficiencies are phenotypic variants of the same genetic disease and that the low plasma concentrations of free protein S in both types are the result of an equimolar relationship between protein S and C4BPβ+.
Nyckelord
- CD4 antigen
- protein S
- warfarin
- adolescent
- adult
- aged
- anticoagulation
- article
- binding affinity
- child
- clinical article
- controlled study
- female
- genetic risk
- human
- human cell
- human tissue
- male
- phenotype
- priority journal
- protein binding
- protein blood level
- protein defect
- protein deficiency
- protein S deficiency
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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