Charles M Rowland1, Clive R Pullinger2, May M Luke3, Dov Shiffman3, Lauri Green4, Irina Movsesyan5, James J Devlin3, Mary J Malloy5, John P Kane5, Anetta Undas6. 1. Celera-A Division of Quest Diagnostics, 1311 Harbor Bay Parkway, Alameda, CA 94502, USA. Electronic address: charles.rowland@celera.com. 2. Cardiovascular Research Institute, UCSF, San Francisco, CA, USA; Department of Physiological Nursing, UCSF, San Francisco, CA, USA. 3. Celera-A Division of Quest Diagnostics, 1311 Harbor Bay Parkway, Alameda, CA 94502, USA. 4. Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF, San Francisco, CA, USA. 5. Cardiovascular Research Institute, UCSF, San Francisco, CA, USA. 6. Institute of Cardiology, Jagiellonian University School of Medicine, Cracow, Poland.
Abstract
INTRODUCTION: Elevated lipoprotein(a) (Lp(a)) levels were reported to be associated with dense fibrin clots. The apo(a) component of Lp(a) is encoded by LPA, and the Met allele of the LPA Ile4399Met polymorphism is associated with elevated Lp(a) levels and cardiovascular disease risk. We investigated whether Ile4399Met was associated with fibrin clot properties. MATERIALS AND METHODS: We determined plasma Lp(a) levels, fibrin clot permeability and lysis time for 64 LPA 4399Met carriers and 128 noncarriers matched for age, sex, ethnicity, and enrollment site. RESULTS: Elevated Lp(a) levels were associated with reduced clot permeability and prolonged lysis time (P<0.0001). Carriers of 4399Met had higher Lp(a) levels compared with noncarriers (P=0.0003). However, this association differed by ethnicity (P=0.003 for interaction between genotype and ethnicity): compared with noncarriers, 4399Met carriers had 2.89 fold higher Lp(a) levels among Caucasians while no difference was observed among non-Caucasians (primarily East Asians and Hispanics). Among all subjects, no association was observed between Ile4399Met and clot properties, but this relationship also differed by ethnicity: among non-Caucasians, 4399Met carriers had increased clot permeability and shorter lysis time; whereas among Caucasians, the trend was for decreased permeability and longer lysis time (P<0.01 for interactions between genotype and ethnicity). CONCLUSIONS: We confirmed that elevated Lp(a) levels are associated with dense fibrin clots, and found that the association of LPA 4399Met carriers and clot permeability as well as lysis time differ by ethnicity.
INTRODUCTION: Elevated lipoprotein(a) (Lp(a)) levels were reported to be associated with dense fibrin clots. The apo(a) component of Lp(a) is encoded by LPA, and the Met allele of the LPA Ile4399Met polymorphism is associated with elevated Lp(a) levels and cardiovascular disease risk. We investigated whether Ile4399Met was associated with fibrin clot properties. MATERIALS AND METHODS: We determined plasma Lp(a) levels, fibrin clot permeability and lysis time for 64 LPA 4399Met carriers and 128 noncarriers matched for age, sex, ethnicity, and enrollment site. RESULTS: Elevated Lp(a) levels were associated with reduced clot permeability and prolonged lysis time (P<0.0001). Carriers of 4399Met had higher Lp(a) levels compared with noncarriers (P=0.0003). However, this association differed by ethnicity (P=0.003 for interaction between genotype and ethnicity): compared with noncarriers, 4399Met carriers had 2.89 fold higher Lp(a) levels among Caucasians while no difference was observed among non-Caucasians (primarily East Asians and Hispanics). Among all subjects, no association was observed between Ile4399Met and clot properties, but this relationship also differed by ethnicity: among non-Caucasians, 4399Met carriers had increased clot permeability and shorter lysis time; whereas among Caucasians, the trend was for decreased permeability and longer lysis time (P<0.01 for interactions between genotype and ethnicity). CONCLUSIONS: We confirmed that elevated Lp(a) levels are associated with dense fibrin clots, and found that the association of LPA 4399Met carriers and clot permeability as well as lysis time differ by ethnicity.
Authors: Michael B Boffa; Tanya T Marar; Calvin Yeang; Nicholas J Viney; Shuting Xia; Joseph L Witztum; Marlys L Koschinsky; Sotirios Tsimikas Journal: J Lipid Res Date: 2019-09-24 Impact factor: 5.922
Authors: Hong Wang; Chan E Hong; Joshua P Lewis; Yanbei Zhu; Xing Wang; Xin Chu; Joshua Backman; Ziying Hu; Peixin Yang; Christopher D Still; Glenn S Gerhard; Mao Fu Journal: G3 (Bethesda) Date: 2016-11-08 Impact factor: 3.154