title: Significant association of urokinase plasminogen activator Pro141Leu with serum lipid profiles in a Japanese population.
abstract: Urokinase plasminogen activator (uPA) plays important physiological and pathological roles in fibrinolysis, cancer metastasis, and atherosclerosis. One study suggested that uPA also has a major role in cholesterol biosynthesis in humans via its receptor uPAR. Thus, we investigated the associations of functional uPA polymorphism (plasminogen activator, urokinase; PLAU Pro141Leu, rs2227564) with serum lipid profiles in a Japanese cohort. The study included 5152 participants (1465 male, 3687 female; age range, 35-69 years) of the Daiko Study, a part of the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). Subjects were enrolled at the Daiko Medical Center from June 2008 to May 2010. Low-density lipoprotein cholesterol (LDL-C) and non-HDL-C (subtraction of high-density lipoprotein cholesterol from total cholesterol) in fasting blood of participants were each classified into two groups, < or ≥ 140 mg/dL, and < or ≥ 170 mg/dL, respectively. Genotype frequencies of PLAU Pro141Leu (rs2227564) were 59.1% for ProPro, 35.6% for ProLeu, and 5.3% for LeuLeu, and were in Hardy-Weinberg equilibrium (p=0.789). The allele frequencies were 0.769 for Pro and 0.231 for Leu. The multivariate-adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for high LDL-C and non-HDL-C were 1.11 (95%CI; 1.00-1.23) and 1.16 (95%CI; 1.03-1.30) for those with Leu allele relative to ProPro. This study suggested that PLAU Pro141Leu (rs2227564) is significantly associated with serum lipid levels in a Japanese population.
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. takashi.tamura@c.mbox.nagoya-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Tamura
authors.forename: Emi
authors.initials: E
authors.lastname: Morita
authors.forename: Sayo
authors.initials: S
authors.lastname: Kawai
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hori
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kondo
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator; D014280:Triglycerides; D014568:Urokinase-Type Plasminogen Activator