Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects

K. Ishii, S. Oguchi, Mitsuru Murata, Y. Mitsuyoshi, E. Takeshita, Daisuke Ito, N. Tanahashi, Y. Fukuuchi, K. Oosumi, K. Matsumoto, M. Kitajima, M. Yamamoto, G. Watanabe, Y. Ikeda, K. Watanabe

Research output: Contribution to journalArticle

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Abstract

Coagulation factor XII (FXII) is activated on contact with various biologic surfaces, including subendothelial tissues and lipoprotein particles. Thus, the plasma level of activated FXII (XIIa) might represent vascular lesions or be a marker of abnormal lipid metabolism. A 46C/T polymorphism was recently described in the FXII gene close to the ATG translation initiation codon, which was associated with inter-individual variation of plasma FXII zymogen levels. The present paper reports the association of the 46C/T polymorphism with plasma XIIa levels in apparently healthy subjects, and in patients with ischemic cerebrovascular disease (CVD) and arteriosclerosis obliterans (ASO). XIIa levels were not significantly different between patients and controls, but were strongly dependent on XII 46C/T genotypes (2.07 ± 0.81, 1.65 ± 0.63, and 0.93 ± 0.41 ng/ml for C/C, C/T, and T/T genotypes, respectively; P< 0.0001). This association was evident for each group studied (P< 0.0001 for CVD and controls; P= 0.0007 for ASO). There were positive correlations between plasma FXII clotting activity and XIIa levels. In a univariate analysis, XIIa correlated with total cholesterol, triglycerides, plasminogen activator inhibitor-1, and C-reactive protein (CRP), although the presence of conventional cardiovascular risk factors (male sex, smoking, hypertension, hypercholesterolemia, diabetes) did not significantly increase XIIa. Stepwise regression analyses revealed that the XII clotting activity had the strongest association with XIIa. In conclusion, XIIa levels depended on XII 46C/T genotype and correlated with some cardiovascular risk factors. Thus, the FXII genotype should be taken into consideration for interpretation of plasma XIIa levels. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalBlood Coagulation and Fibrinolysis
Volume11
Issue number3
Publication statusPublished - 2000

Fingerprint

Factor XIIa
Factor XII
Enzyme Precursors
Healthy Volunteers
Genotype
Arteriosclerosis Obliterans
Cerebrovascular Disorders
Initiator Codon
Plasminogen Activator Inhibitor 1
Hypercholesterolemia
Lipid Metabolism
C-Reactive Protein
Lipoproteins
Blood Vessels
Triglycerides
Smoking
Cholesterol
Regression Analysis
vascular factor
Hypertension

Keywords

  • Activated factor XII
  • Arteriosclerosis obliterans
  • Atherosclerosis
  • Cerebrovascular diseases
  • Coagulation factor XII
  • Genetics
  • Polymorphism
  • Risk factors

ASJC Scopus subject areas

  • Hematology

Cite this

Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects. / Ishii, K.; Oguchi, S.; Murata, Mitsuru; Mitsuyoshi, Y.; Takeshita, E.; Ito, Daisuke; Tanahashi, N.; Fukuuchi, Y.; Oosumi, K.; Matsumoto, K.; Kitajima, M.; Yamamoto, M.; Watanabe, G.; Ikeda, Y.; Watanabe, K.

In: Blood Coagulation and Fibrinolysis, Vol. 11, No. 3, 2000, p. 277-284.

Research output: Contribution to journalArticle

Ishii, K, Oguchi, S, Murata, M, Mitsuyoshi, Y, Takeshita, E, Ito, D, Tanahashi, N, Fukuuchi, Y, Oosumi, K, Matsumoto, K, Kitajima, M, Yamamoto, M, Watanabe, G, Ikeda, Y & Watanabe, K 2000, 'Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects', Blood Coagulation and Fibrinolysis, vol. 11, no. 3, pp. 277-284.
Ishii, K. ; Oguchi, S. ; Murata, Mitsuru ; Mitsuyoshi, Y. ; Takeshita, E. ; Ito, Daisuke ; Tanahashi, N. ; Fukuuchi, Y. ; Oosumi, K. ; Matsumoto, K. ; Kitajima, M. ; Yamamoto, M. ; Watanabe, G. ; Ikeda, Y. ; Watanabe, K. / Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects. In: Blood Coagulation and Fibrinolysis. 2000 ; Vol. 11, No. 3. pp. 277-284.
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abstract = "Coagulation factor XII (FXII) is activated on contact with various biologic surfaces, including subendothelial tissues and lipoprotein particles. Thus, the plasma level of activated FXII (XIIa) might represent vascular lesions or be a marker of abnormal lipid metabolism. A 46C/T polymorphism was recently described in the FXII gene close to the ATG translation initiation codon, which was associated with inter-individual variation of plasma FXII zymogen levels. The present paper reports the association of the 46C/T polymorphism with plasma XIIa levels in apparently healthy subjects, and in patients with ischemic cerebrovascular disease (CVD) and arteriosclerosis obliterans (ASO). XIIa levels were not significantly different between patients and controls, but were strongly dependent on XII 46C/T genotypes (2.07 ± 0.81, 1.65 ± 0.63, and 0.93 ± 0.41 ng/ml for C/C, C/T, and T/T genotypes, respectively; P< 0.0001). This association was evident for each group studied (P< 0.0001 for CVD and controls; P= 0.0007 for ASO). There were positive correlations between plasma FXII clotting activity and XIIa levels. In a univariate analysis, XIIa correlated with total cholesterol, triglycerides, plasminogen activator inhibitor-1, and C-reactive protein (CRP), although the presence of conventional cardiovascular risk factors (male sex, smoking, hypertension, hypercholesterolemia, diabetes) did not significantly increase XIIa. Stepwise regression analyses revealed that the XII clotting activity had the strongest association with XIIa. In conclusion, XIIa levels depended on XII 46C/T genotype and correlated with some cardiovascular risk factors. Thus, the FXII genotype should be taken into consideration for interpretation of plasma XIIa levels. (C) 2000 Lippincott Williams and Wilkins.",
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T1 - Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects

AU - Ishii, K.

AU - Oguchi, S.

AU - Murata, Mitsuru

AU - Mitsuyoshi, Y.

AU - Takeshita, E.

AU - Ito, Daisuke

AU - Tanahashi, N.

AU - Fukuuchi, Y.

AU - Oosumi, K.

AU - Matsumoto, K.

AU - Kitajima, M.

AU - Yamamoto, M.

AU - Watanabe, G.

AU - Ikeda, Y.

AU - Watanabe, K.

PY - 2000

Y1 - 2000

N2 - Coagulation factor XII (FXII) is activated on contact with various biologic surfaces, including subendothelial tissues and lipoprotein particles. Thus, the plasma level of activated FXII (XIIa) might represent vascular lesions or be a marker of abnormal lipid metabolism. A 46C/T polymorphism was recently described in the FXII gene close to the ATG translation initiation codon, which was associated with inter-individual variation of plasma FXII zymogen levels. The present paper reports the association of the 46C/T polymorphism with plasma XIIa levels in apparently healthy subjects, and in patients with ischemic cerebrovascular disease (CVD) and arteriosclerosis obliterans (ASO). XIIa levels were not significantly different between patients and controls, but were strongly dependent on XII 46C/T genotypes (2.07 ± 0.81, 1.65 ± 0.63, and 0.93 ± 0.41 ng/ml for C/C, C/T, and T/T genotypes, respectively; P< 0.0001). This association was evident for each group studied (P< 0.0001 for CVD and controls; P= 0.0007 for ASO). There were positive correlations between plasma FXII clotting activity and XIIa levels. In a univariate analysis, XIIa correlated with total cholesterol, triglycerides, plasminogen activator inhibitor-1, and C-reactive protein (CRP), although the presence of conventional cardiovascular risk factors (male sex, smoking, hypertension, hypercholesterolemia, diabetes) did not significantly increase XIIa. Stepwise regression analyses revealed that the XII clotting activity had the strongest association with XIIa. In conclusion, XIIa levels depended on XII 46C/T genotype and correlated with some cardiovascular risk factors. Thus, the FXII genotype should be taken into consideration for interpretation of plasma XIIa levels. (C) 2000 Lippincott Williams and Wilkins.

AB - Coagulation factor XII (FXII) is activated on contact with various biologic surfaces, including subendothelial tissues and lipoprotein particles. Thus, the plasma level of activated FXII (XIIa) might represent vascular lesions or be a marker of abnormal lipid metabolism. A 46C/T polymorphism was recently described in the FXII gene close to the ATG translation initiation codon, which was associated with inter-individual variation of plasma FXII zymogen levels. The present paper reports the association of the 46C/T polymorphism with plasma XIIa levels in apparently healthy subjects, and in patients with ischemic cerebrovascular disease (CVD) and arteriosclerosis obliterans (ASO). XIIa levels were not significantly different between patients and controls, but were strongly dependent on XII 46C/T genotypes (2.07 ± 0.81, 1.65 ± 0.63, and 0.93 ± 0.41 ng/ml for C/C, C/T, and T/T genotypes, respectively; P< 0.0001). This association was evident for each group studied (P< 0.0001 for CVD and controls; P= 0.0007 for ASO). There were positive correlations between plasma FXII clotting activity and XIIa levels. In a univariate analysis, XIIa correlated with total cholesterol, triglycerides, plasminogen activator inhibitor-1, and C-reactive protein (CRP), although the presence of conventional cardiovascular risk factors (male sex, smoking, hypertension, hypercholesterolemia, diabetes) did not significantly increase XIIa. Stepwise regression analyses revealed that the XII clotting activity had the strongest association with XIIa. In conclusion, XIIa levels depended on XII 46C/T genotype and correlated with some cardiovascular risk factors. Thus, the FXII genotype should be taken into consideration for interpretation of plasma XIIa levels. (C) 2000 Lippincott Williams and Wilkins.

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KW - Arteriosclerosis obliterans

KW - Atherosclerosis

KW - Cerebrovascular diseases

KW - Coagulation factor XII

KW - Genetics

KW - Polymorphism

KW - Risk factors

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