Activated factor XII levels and factor XII 46C>T genotype in relation to coronary artery calcification in patients with type 1 diabetes and healthy subjects

Helen M. Colhoun, Francesco Zito, N. Norman Chan, Michael B. Rubens, John H. Fuller, Steve E. Humphries

    Research output: Contribution to journalArticle

    35 Citations (Scopus)

    Abstract

    The relationship of activated factor XII (FXIIa) and FXII 46C>T genotype to coronary atherosclerosis and endothelial function was examined in 192 randomly sampled subjects from the general population and 190 type 1 diabetic subjects (mean age 38±4 years). Coronary artery calcification (CAC) was measured using Electron beam CT. von Willebrand factor (vWF), a marker of endothelial function, and FXIIa were measured by ELISA. Endothelial nitric oxide production was quantified as the forearm blood flow response to intra-brachial infusion of bradykinin and NG monomethyl-l-arginine (l-NMMA). A higher FXIIa was independently associated with higher triglycerides (P<0.001), BMI (P=0.001), alcohol consumption (P=0.003) and vWF (P<0.001) in non-diabetic subjects and with insulin dose (P=0.009), total cholesterol (P=0.02) and alcohol (P<0.001) in diabetic subjects. Diabetic subjects had lower FXIIa (1.55 ng/ml) than non-diabetic subjects (1.92 ng/ml, P<0.001). Higher FXIIa was associated with lower response to bradykinin (P=0.048) and to l-NMMA (P=0.029). FXIIa was positively associated with CAC (odds ratio=1.57 for every 1 ng/ml higher FXIIa, P=0.005) but not independently of other risk factors (odds ratio=1.1 on adjustment). 46C>T genotype explained 18% of the variance in FXIIa (P<0.001) but was not associated with CAC (P=0.6). We conclude that plasma FXIIa is under strong genetic control but also reflects plasma triglycerides and endothelial activation or dysfunction. FXIIa appears unlikely to be directly atherogenic but may be a useful marker of coronary atherosclerosis because of its association with these other factors. Type 1 diabetes is associated with lower levels of FXIIa despite a greater prevalence of atherosclerosis.

    Original languageEnglish
    Pages (from-to)363-369
    Number of pages7
    JournalAtherosclerosis
    Volume163
    Issue number2
    DOIs
    Publication statusPublished - Aug 2002

    Fingerprint

    Factor XIIa
    Factor XII
    Type 1 Diabetes Mellitus
    Coronary Artery Disease
    Coronary Vessels
    Healthy Volunteers
    Triglycerides
    Genotype
    von Willebrand Factor
    Bradykinin
    Forearm
    Arginine
    Atherosclerosis
    Nitric Oxide
    Arm
    Enzyme-Linked Immunosorbent Assay
    Electrons
    Population

    Cite this

    Colhoun, Helen M. ; Zito, Francesco ; Chan, N. Norman ; Rubens, Michael B. ; Fuller, John H. ; Humphries, Steve E. / Activated factor XII levels and factor XII 46C>T genotype in relation to coronary artery calcification in patients with type 1 diabetes and healthy subjects. In: Atherosclerosis. 2002 ; Vol. 163, No. 2. pp. 363-369.
    @article{c4e9a3f1a47946fa8f58475b4d2fc160,
    title = "Activated factor XII levels and factor XII 46C>T genotype in relation to coronary artery calcification in patients with type 1 diabetes and healthy subjects",
    abstract = "The relationship of activated factor XII (FXIIa) and FXII 46C>T genotype to coronary atherosclerosis and endothelial function was examined in 192 randomly sampled subjects from the general population and 190 type 1 diabetic subjects (mean age 38±4 years). Coronary artery calcification (CAC) was measured using Electron beam CT. von Willebrand factor (vWF), a marker of endothelial function, and FXIIa were measured by ELISA. Endothelial nitric oxide production was quantified as the forearm blood flow response to intra-brachial infusion of bradykinin and NG monomethyl-l-arginine (l-NMMA). A higher FXIIa was independently associated with higher triglycerides (P<0.001), BMI (P=0.001), alcohol consumption (P=0.003) and vWF (P<0.001) in non-diabetic subjects and with insulin dose (P=0.009), total cholesterol (P=0.02) and alcohol (P<0.001) in diabetic subjects. Diabetic subjects had lower FXIIa (1.55 ng/ml) than non-diabetic subjects (1.92 ng/ml, P<0.001). Higher FXIIa was associated with lower response to bradykinin (P=0.048) and to l-NMMA (P=0.029). FXIIa was positively associated with CAC (odds ratio=1.57 for every 1 ng/ml higher FXIIa, P=0.005) but not independently of other risk factors (odds ratio=1.1 on adjustment). 46C>T genotype explained 18{\%} of the variance in FXIIa (P<0.001) but was not associated with CAC (P=0.6). We conclude that plasma FXIIa is under strong genetic control but also reflects plasma triglycerides and endothelial activation or dysfunction. FXIIa appears unlikely to be directly atherogenic but may be a useful marker of coronary atherosclerosis because of its association with these other factors. Type 1 diabetes is associated with lower levels of FXIIa despite a greater prevalence of atherosclerosis.",
    author = "Colhoun, {Helen M.} and Francesco Zito and Chan, {N. Norman} and Rubens, {Michael B.} and Fuller, {John H.} and Humphries, {Steve E.}",
    year = "2002",
    month = "8",
    doi = "10.1016/S0021-9150(02)00022-9",
    language = "English",
    volume = "163",
    pages = "363--369",
    journal = "Atherosclerosis",
    issn = "0021-9150",
    publisher = "Elsevier",
    number = "2",

    }

    Activated factor XII levels and factor XII 46C>T genotype in relation to coronary artery calcification in patients with type 1 diabetes and healthy subjects. / Colhoun, Helen M.; Zito, Francesco; Chan, N. Norman; Rubens, Michael B.; Fuller, John H.; Humphries, Steve E.

    In: Atherosclerosis, Vol. 163, No. 2, 08.2002, p. 363-369.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Activated factor XII levels and factor XII 46C>T genotype in relation to coronary artery calcification in patients with type 1 diabetes and healthy subjects

    AU - Colhoun, Helen M.

    AU - Zito, Francesco

    AU - Chan, N. Norman

    AU - Rubens, Michael B.

    AU - Fuller, John H.

    AU - Humphries, Steve E.

    PY - 2002/8

    Y1 - 2002/8

    N2 - The relationship of activated factor XII (FXIIa) and FXII 46C>T genotype to coronary atherosclerosis and endothelial function was examined in 192 randomly sampled subjects from the general population and 190 type 1 diabetic subjects (mean age 38±4 years). Coronary artery calcification (CAC) was measured using Electron beam CT. von Willebrand factor (vWF), a marker of endothelial function, and FXIIa were measured by ELISA. Endothelial nitric oxide production was quantified as the forearm blood flow response to intra-brachial infusion of bradykinin and NG monomethyl-l-arginine (l-NMMA). A higher FXIIa was independently associated with higher triglycerides (P<0.001), BMI (P=0.001), alcohol consumption (P=0.003) and vWF (P<0.001) in non-diabetic subjects and with insulin dose (P=0.009), total cholesterol (P=0.02) and alcohol (P<0.001) in diabetic subjects. Diabetic subjects had lower FXIIa (1.55 ng/ml) than non-diabetic subjects (1.92 ng/ml, P<0.001). Higher FXIIa was associated with lower response to bradykinin (P=0.048) and to l-NMMA (P=0.029). FXIIa was positively associated with CAC (odds ratio=1.57 for every 1 ng/ml higher FXIIa, P=0.005) but not independently of other risk factors (odds ratio=1.1 on adjustment). 46C>T genotype explained 18% of the variance in FXIIa (P<0.001) but was not associated with CAC (P=0.6). We conclude that plasma FXIIa is under strong genetic control but also reflects plasma triglycerides and endothelial activation or dysfunction. FXIIa appears unlikely to be directly atherogenic but may be a useful marker of coronary atherosclerosis because of its association with these other factors. Type 1 diabetes is associated with lower levels of FXIIa despite a greater prevalence of atherosclerosis.

    AB - The relationship of activated factor XII (FXIIa) and FXII 46C>T genotype to coronary atherosclerosis and endothelial function was examined in 192 randomly sampled subjects from the general population and 190 type 1 diabetic subjects (mean age 38±4 years). Coronary artery calcification (CAC) was measured using Electron beam CT. von Willebrand factor (vWF), a marker of endothelial function, and FXIIa were measured by ELISA. Endothelial nitric oxide production was quantified as the forearm blood flow response to intra-brachial infusion of bradykinin and NG monomethyl-l-arginine (l-NMMA). A higher FXIIa was independently associated with higher triglycerides (P<0.001), BMI (P=0.001), alcohol consumption (P=0.003) and vWF (P<0.001) in non-diabetic subjects and with insulin dose (P=0.009), total cholesterol (P=0.02) and alcohol (P<0.001) in diabetic subjects. Diabetic subjects had lower FXIIa (1.55 ng/ml) than non-diabetic subjects (1.92 ng/ml, P<0.001). Higher FXIIa was associated with lower response to bradykinin (P=0.048) and to l-NMMA (P=0.029). FXIIa was positively associated with CAC (odds ratio=1.57 for every 1 ng/ml higher FXIIa, P=0.005) but not independently of other risk factors (odds ratio=1.1 on adjustment). 46C>T genotype explained 18% of the variance in FXIIa (P<0.001) but was not associated with CAC (P=0.6). We conclude that plasma FXIIa is under strong genetic control but also reflects plasma triglycerides and endothelial activation or dysfunction. FXIIa appears unlikely to be directly atherogenic but may be a useful marker of coronary atherosclerosis because of its association with these other factors. Type 1 diabetes is associated with lower levels of FXIIa despite a greater prevalence of atherosclerosis.

    U2 - 10.1016/S0021-9150(02)00022-9

    DO - 10.1016/S0021-9150(02)00022-9

    M3 - Article

    VL - 163

    SP - 363

    EP - 369

    JO - Atherosclerosis

    JF - Atherosclerosis

    SN - 0021-9150

    IS - 2

    ER -