Effect of Two Lipoprotein (a)-Associated Genetic Variants on Plasminogen Levels and Fibrinolysis.
Two genetic variants (rs3798220 and rs10455872) in the apolipoprotein (a) gene (LPA) have been implicated in cardiovascular disease (CVD), presumably through their association with lipoprotein (a) [Lp(a)] levels. While Lp(a) is recognized as a lipoprotein with atherogenic and thrombogenic characteristics, it is unclear whether or not the two Lp(a)-associated genetic variants are also associated with markers of thrombosis (i.e., plasminogen levels and fibrinolysis). In the present study, we genotyped the two genetic variants in 2919 subjects of the Old Order Amish (OOA) and recruited 146 subjects according to the carrier and noncarrier status for rs3798220 and rs10455872, and also matched for gender and age. We measured plasma Lp(a) and plasminogen levels in these subjects, and found that the concentrations of plasma Lp(a) were 2.62- and 1.73-fold higher in minor allele carriers of rs3798220 and rs10455872, respectively, compared with noncarriers (P= 2.04 × 10-17andP= 1.64 × 10-6, respectively). By contrast, there was no difference in plasminogen concentrations between carriers and noncarriers of rs3798220 and rs10455872. Furthermore, we observed no association between carrier status of rs3798220 or rs10455872 with clot lysis time. Finally, plasminogen mRNA expression in liver samples derived from 76 Caucasian subjects was not significantly different between carriers and noncarriers of these two genetic variants. Our results provide further insight into the mechanism of action behind two genetic variants previously implicated in CVD risk and show that these polymorphisms are not major modulating factors for plasma plasminogen levels and fibrinolysis.
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Hong
H
Wang
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Chan E
CE
Hong
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Joshua P
JP
Lewis
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Yanbei
Y
Zhu
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201.|Department of Orthopedic Surgery, Second Affiliated Hospital of Chongqing Medical University, 400010, China.
Xing
X
Wang
Geisinger Obesity Institute, Geisinger Clinic, Danville, Pennsylvania 17822.
Xin
X
Chu
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Joshua
J
Backman
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Ziying
Z
Hu
Department of Obstetrics, Gynecology, & Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Peixin
P
Yang
Geisinger Obesity Institute, Geisinger Clinic, Danville, Pennsylvania 17822.
Christopher D
CD
Still
Geisinger Obesity Institute, Geisinger Clinic, Danville, Pennsylvania 17822.|Penn State Institute for Personalized Medicine, Penn State College of Medicine, Hershey, Pennsylvania 17033.
Glenn S
GS
Gerhard
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201 mfu@medicine.umaryland.edu.
Mao
http://orcid.org/0000-0002-9904-5537
M
Fu
fibrinolysis; genetics; lipoprotein (a); plasminogen; thrombogenicity