Abstract
Plasma kallikrein formed from prekallikrein (PK) produces bradykinin from kininogens and activates factor XII. Plasma PK is activated by factors αXIIa, βXIIa, or prolylcarboxypeptidase (PRCP). A cross-sectional investigation determined if there is an association of PRCP and KLKB1 polymorphisms with cardiovascular disease (CVD). DNA was obtained from 2243 individuals from the Prevention of Events with Angiotensin Converting Enzyme trial. Two PRCP SNPs, rs7104980 and rs2298668, and two KLKB1 SNPs, rs3733402 and rs3087505, were genotyped. Logistic regression models were performed for history of diabetes, myocardial infarction, stroke, angina, angiographic coronary disease, CABG, intermittent claudication, percutaneous transluminal coronary angioplasty (PTCA), and transient ischemic attack. The PRCP SNP rs7104980 increased the odds of having a history of PTCA by 21% [odds ratio (OR) = 1.211; 95% confidence intervals (CI) = (1.008, 1.454)]; P = 0.041, but was non-significant after Bonferroni correction. Alternatively, having the G allele for rs3733402 (KLKB1 gene) decreased the odds of having a history of angiographic coronary disease by 24% [OR = 0.759; 95% CI = (0.622, 0.927)]; P = 0.007 that was statistically significant (P < 0.01) after Bonferroni correction for multiple hypothesis testing. When the best-fit model based on the Akaike information criterion controlled for age, weight, gender, hypertension, and history of angina, the G allele of KLKB1 rs3733402 that is associated with less plasma kallikrein activity correlated with reduced history of CVD.
Highlights
Plasma prekallikrein (PK) is a zymogen whose enzyme plasma kallikrein is known to initiate and amplify factor XII activation on collagen and polyphosphates in plasma in the intravascular compartment to activate intrinsic blood coagulation
plasma prekallikrein gene (KLKB1) rs3087505 is associated with venous thrombosis and this SNP is in linkage disequilibrium (LD) with two F11 SNPs associated with thromboembolism [1, 2]
The present cross-sectional study suggests that a polymorphism in KLKB1 associated with reduced PK binding to high molecular weight kininogen (HK) leading to a less actable zymogen is associated with reduced cardiovascular disease (CVD)
Summary
Plasma prekallikrein (PK) is a zymogen whose enzyme plasma kallikrein is known to initiate and amplify factor XII activation on collagen and polyphosphates in plasma in the intravascular compartment to activate intrinsic blood coagulation. Formed plasma kallikrein is the major enzyme to generate bradykinin from high molecular weight kininogen (HK) and to convert plasminogen. Recent studies with klkb1−/− mice indicate that animals lacking klkb have delayed arterial thrombosis not due to reduced contact activation but due to reduced vessel wall tissue factor [6, 7]. These combined studies suggest that PK contributes to vascular homeostasis. Previous work by our own group demonstrated that elevated plasma PK correlates with accelerated vascular disease and proteinuria in a large population of diabetic patients [8, 9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
