Significant association of urokinase plasminogen activator Pro141Leu with serum lipid profiles in a Japanese population |
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Authors: | Takashi Tamura Emi Morita Sayo Kawai Rieko Okada Mariko Naito Kenji Wakai Yoko Hori Takaaki Kondo Nobuyuki Hamajima |
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Affiliation: | 1. Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan;2. Nagoya University School of Health Science, Nagoya 461-8673, Japan |
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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. |
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Keywords: | BMI, body mass index CI, confidence interval ECM, extracellular matrix HDL-C, high-density lipoprotein cholesterol HGMCR, 3-hydroxy-3-methylglutaryl CoA reductase J-MICC, Japan Multi-Institutional Collaborative Cohort LDL-C, low-density lipoprotein cholesterol MAF, minor allele frequency OR, odds ratio PCR, polymerase chain reaction PLAU, plasminogen activator, urokinase PLAUR, PLAU receptor SD, standard deviation SE, standard error SNP, single nucleotide polymorphism TC, total cholesterol TG, triglycerides uPA, urokinase plasminogen activator uPAR, uPA receptor |
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