TY - JOUR
T1 - A cross-sectional study of KLKB1 and PRCP polymorphisms in patient samples with cardiovascular disease
AU - Gittleman, Haley R.
AU - Merkulova, Alona
AU - Alhalabi, Omar
AU - Stavrou, Evi X.
AU - Veigl, Martina L.
AU - Barnholtz-Sloan, Jill S.
AU - Schmaier, Alvin H.
N1 - Publisher Copyright:
© 2016 Gittleman, Merkulova, Alhalabi, Stavrou, Veigl, Barnholtz-Sloan and Schmaier.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Cardiovascular disease
KW - High molecular weight kininogen
KW - KLKB1
KW - PRCP
KW - Prekallikrein
KW - Prolylcarboxypeptidase
UR - http://www.scopus.com/inward/record.url?scp=84980715443&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84980715443&partnerID=8YFLogxK
U2 - 10.3389/fmed.2016.00017
DO - 10.3389/fmed.2016.00017
M3 - Article
C2 - 27200353
AN - SCOPUS:84980715443
SN - 2296-858X
VL - 3
JO - Frontiers in Medicine
JF - Frontiers in Medicine
IS - APR
M1 - 17
ER -