title: A Cross-sectional Study of KLKB1 and PRCP Polymorphisms in Patient Samples with Cardiovascular Disease.
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.
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University , Cleveland, OH , USA.
authors.forename: Haley R
authors.initials: HR
authors.lastname: Gittleman
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Case Western Reserve University , Cleveland, OH , USA.
authors.forename: Alona
authors.initials: A
authors.lastname: Merkulova
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Case Western Reserve University , Cleveland, OH , USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Alhalabi
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Case Western Reserve University, Cleveland, OH, USA; Louis Stokes Veterans Administration Hospital, Cleveland, OH, USA.
authors.forename: Evi X
authors.initials: EX
authors.lastname: Stavrou
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University , Cleveland, OH , USA.
authors.forename: Martina L
authors.initials: ML
authors.lastname: Veigl
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University , Cleveland, OH , USA.
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, Division of Hematology-Oncology, Case Western Reserve University, Cleveland, OH, USA; University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Alvin H
authors.initials: AH
authors.lastname: Schmaier
keywords: KLKB1; PRCP; cardiovascular disease; high molecular weight kininogen; prekallikrein; prolylcarboxypeptidase