Significant association of
urokinase plasminogen activator Pro141Leu
with serum lipid profiles in a Japanese population
Pro141Leu
‫ޤ܂ޣ‬
࠙ࡠࠠ࠽࡯࠯ဳࡊ࡜ࠬࡒࡁ࡯ࠥࡦࠕࠢ࠴ࡌ࡯࠲࡯(uPA)ߪࡊ࡜ࠬࡒࡦࠍ‫ݳ‬ዉߔࠆߎ
ߣߦࠃࠅ⚵aౝṁ♽ࠍଦ੤ߒ‫ޔ‬Ἳ∝෻ᔕߦᷓߊീࠊߞߡ޿ࠆ‫ޕ‬෶‫ࠕ࠹ࡠࡊࡠ࠲ࡔޔ‬
࡯࠯ࠍ‫ݳ‬ዉߔࠆߎߣߦࠃࠅ⚦ƙᄖࡑ࠻࡝࠶ࠢࠬߩ⎕უࠍଦ੤ߒ‫ߩࠎ߇ޔ‬ঙ⒖࡮ᶐẢࠍ
ଦߔ୰‫ߥۀ‬ಽሶߣߒߡႎ๔ߐࠇߡ޿ࠆ‫ޕ‬2007 ᐕ‫ޔ‬Fuhrman ࠄߪ uPA ߣߘߩ․⇣⊛ߥฃ
ኈ૕(uPAR)ߣߩ⋧੕૞↪߇ࡅ࠻ߩࠦ࡟ࠬ࠹ࡠ࡯࡞↢วᚑࠍଦ੤ߐߖࠆ੐ࠍႎ๔ߒߚ‫ޕ‬
෶‫ޔ‬หႎ๔ߪ uPA-uPAR ⋧੕૞↪߇ࡅ࠻ߩࠦ࡟ࠬ࠹ࡠ࡯࡞↢วᚑߩਥߚࠆ⚻ऍߢ޽ࠆ
ࡔࡃࡠࡦ଴⚻ऍߦᓇະࠍਈ߃ߡ޿ࠆ੐ࠍᒝߊ␜ໂߒߡ޿ߚ‫ޕ‬
ߘߎߢ‫⎇ᧄޔ‬ⓥߢߪ uPA ߩਃᰴ᭴੗ߦᄌൻࠍ෸߷ߒ‫ޔ‬ၮࢠ߳ߩۛ๺ᕈߦᄌൻࠍ߽ߚ
ࠄߔ੐߇ႎ๔ߐࠇߡ޿ࠆ৻ࠕࡒࡁ଴¾឵ࠍ઻߁ SNP (plasminogen activator, urokinase;
PLAU Pro141Leu, rs2227564)߇ታ෉ߩࡅ࠻‫׺‬ᷡƭࢠỚᐲߦᓇະࠍਈ߃ߡ޿ࠆ߆ߤ߁߆‫ޔ‬
ᣣᧄੱߩ৻ɨ෨࿅ߦ߅޿ߡᬌ‫ࠍ܋‬؅ߞߚ‫ޕ‬
‫ޣ‬ኻ࠾‫ޤ‬
ᧄ⎇ⓥߪ‫↢࡮ࠎ߇ޔ‬ᵴüᘠ∛ߩ⊒∝ߦ߅ߌࠆઞવ⊛‫ۀ‬࿃ߣ↢ᵴⅣႺ‫ۀ‬࿃ߩ੤੕૞↪
ࠍᬌ‫ߦ߼ߚࠆߔ܋‬ታᣉߐࠇߡ޿ࠆࠥࡁࡓࠦ࡯ࡎ࡯࠻⎇ⓥߢ޽ࠆᣣᧄᄙᣉ‫౒ܣ‬หࠦ࡯ࡎ
࡯࠻⎇ⓥ(Japan Multi-Institutional Collaborative Cohort Study; J-MICC Study)ߩ৻࿾඙ߦ
޽ߚࠆᄢᐘ࿾඙ߦ߅ߌࠆࡌ࡯ࠬ࡜ࠗࡦ‫ގ‬ᩏߩ࠺࡯࠲ࠍ↪޿ߚ‫⎇ޕ‬ⓥኻ࠾Ěߪ‫ޔ‬ฬฎደ
Ꮢౝߦ૑᳃␿߇޽ࠆ 35ޯ69 ᱦߩ 5,152 ฬ(↵ᕈ; 1,465 ฬ, ᅚᕈ; 3,687 ฬ)ߢ޽ࠆ‫ޕ‬2008
ᐕ 6 ᦬߆ࠄ 2010 ᐕ 5 ᦬߹ߢ൐෨ࠍ؅޿‫⎇ޔ‬ⓥ‫ށ‬᣿߅ࠃ߮ઞવሶ۳ᨆࠍ฽߼ߚหᗧขᓧ
ࠍታᣉߒߚ‫ޕ‬
‫ޣ‬ᣇᴺ‫ޤ‬
DNA ߪࡃࡈࠖ࡯ࠦ࡯࠻ࠃࠅ᛽಴ߒ‫ޔ‬SNP ߩ᷹ቯߦߪ polymerase chain reaction with
confronting two-pair primers (PCR-CTPP)ᴺࠍ↪޿ߚ‫ޕ‬ኻ࠾Ěߪ⎇ⓥෳടᣣߩ೨ᣣߩᄕ༙
ࠍ៨ขߒߡ߅ࠄߕ‫ߩߘޔ‬ùᦺߩⓨǫᤨᧃ᪳‫ࠍ׺‬ណขߒߚ‫ޕ‬ȴ‫ܕ‬ᑼ‫ގ‬ᩏ␿ߦࠃߞߡ‫ޔ‬༦
ଜ ࡮ ༛ᾍ ü ᘠ ࠍ ⏕ ‫( ࡞ ࡯ ࡠ ࠹ ࠬ ࡟ ࠦ ޕ ߚ ߒ ݪ‬TC), ဎ ኒ ᐲ࡝ ࡐԞ ⊕ ࠦ࡟ ࠬ࠹ ࡠ ࡯࡞
(HDL-C), ਛ ᕈ ƭ ż(TG)ߪ ߘ ࠇ ߙ ࠇ ‫࡞ ࡯ ࡠ ࠹ ࠬ ࡟ ࠦ ޔ‬Dž ᳓ ⚛ ଲ ⚛-⚡ ᄖᴺ, ⋥ធᴺ ,
GK-GPO࡮੶෼ࠣ࡝࠮ࡠ࡯࡞ᶖ෰ᴺࠍ↪޿ߡ᷹ቯߒߚ‫ޕ‬ૐኒᐲ࡝ࡐԞ⊕ࠦ࡟ࠬ࠹ࡠ࡯
࡞(LDL-C)ߪ⋥ធߩ᷹ቯࠍታᣉߖߕ‫ޔ‬TG ߇ 400 mg/dL ᧂḩߩኻ࠾Ě 5,110 ฬ(↵ᕈ; 1,430
ฬ, ᅚᕈ; 3,680 ฬ)ߦඒࠅ‫ޔ‬Friedewald ߩផቯᑼ LDL-C=TC-HDL-(TG/5)ߢផቯߒߚ‫ޕ‬
Non-HDL-C ߪ‫ޔ‬TC ߆ࠄ HDL-C ࠍᷫߓࠆߎߣߦࠃࠅ▚಴ߒߚ‫ޕ‬ᣣᧄേƲ⎬ൻቇળ߇ቯ
߼ߡ޿ࠆၮḰ୯ࠍࠞ࠶࠻ࠝࡈ୯ߣߒߡ↪޿ߡ‫ޔ‬TC, LDL-C, HDL-C, non-HDL-C, TG ࠍ
ߘࠇߙࠇ‫ <ޔ‬or ≥ 220 mg/dL, < or ≥ 140 mg/dL, < or ≥ 40 mg/dL, < or ≥ 170 mg/dL, < or ≥
150 mg/dL ߩੑâߦಽ໳ߒ‫ޔ‬ƭࢠ⇣Ᏹ∝ࠍቯåߒߚ‫ޕ‬BMI ߪ૕୰(kg)ࠍॺണߩੑਸ਼(m 2 )
ߢචߒ‫▚ޔ‬಴ߒߚ‫࡞࡟ࠕޕ‬໛ᐲߪࠞࠗੑਸ਼ᴺࠍ↪޿ߡ Hardy-Weinberg ᐔ‫(ؗ‬HWE)ࠍ⏕
‫ޕߚߒݪ‬ઞવሶဳശߦ߅ߌࠆᐔဋ୯ߩᏅߪ‫৻ޔ‬రଙ¾ಽᢔಽᨆࠍ↪޿ߡᬌቯߒߚ‫׺ޕ‬
ᷡƭࢠỚᐲߩᄙᄌ୲‫ގ‬ᢛᷣߺᐔဋ୯ߪ౒ಽᢔಽᨆࠍ↪޿ߡផቯߒ‫ޔ‬ઞવሶဳശߩᏅࠍ
-1-
ᬌቯߒߚ‫ޔߡ޿↪ࠍ࡞࠺ࡕࠢ࠶ࠖ࠹ࠬࠫࡠޕ‬ᕈ࡮ᐕቲ࡮༦ଜ߅ࠃ߮༛ᾍüᘠ࡮BMI࡮
ƭࢠඐਅ೷ߩ᦯↪ࠍ੤⛊‫ۀ‬࿃ߣߒߡ‫ގ‬ᢛߒ‫ޔ‬ProPro ߦኻߔࠆࡑࠗ࠽࡯ࠕ࡟࡞ Leu ߦ߅
ߌࠆƭࢠ⇣Ᏹ∝ߩࠝ࠶࠭Ყ(ORs)ࠍផቯߒߚ‫᦭ޕ‬ᗧ᳓Ḱࠍ p<0.05 ߣߒߚ‫ޕ‬
‫⚿ޣ‬ᨐ‫ޤ‬
ኻ࠾Ěߪ↵ᕈ 28.4%, ᅚᕈ 71.6%ߢ޽ࠅ‫ోޔ‬૕ߩᐔဋᐕቲߪ 52.5 ᱦߢ޽ߞߚ‫ޕ‬ઞવ
ሶဳ໛ᐲߪ ProPro, ProLeu, LeuLeu ߘࠇߙࠇߢ 59.1%, 35.6%, 5.3%ߢ޽ߞߚ‫࡞࡟ࠕޕ‬໛
ᐲߪ Pro, Leu ߘࠇߙࠇߢ 0.769, 0.231 ߢ޽ࠅ‫ޔ‬HWE ߦᓥߞߡ޿ߚ(p=0.789)‫ޕ‬ƭࢠඐਅ
೷᦯↪Ěߪో૕ߢ 443 ฬ(8.6%)߅ࠅ‫ޔ‬ઞવሶဳശߩƭࢠඐਅ೷᦯↪Ěߩഀวߪ‫ోޔ‬૕
(χ2=0.80, p=0.669), ↵ᕈ(χ 2=1.35, p=0.509), ᅚᕈ(χ 2=0.19, p=0.908)ߢ᦭ᗧߥᏅߪ‫ࠇࠄۇ‬
ߥ߆ߞߚ‫ޕ‬ઞવሶဳശߩ BMI ᐔဋ୯ߪ‫ోޔ‬૕(p=0.019), ᅚᕈ(p=0.007)ߢ᦭ᗧߥᏅ߇‫ۇ‬
ࠄࠇߚ߇‫↵ޔ‬ᕈ(p=0.864)ߢߪ᦭ᗧߥᏅߪ‫ޕߚߞ߆ߥࠇࠄۇ‬
ઞવሶဳശߦ߅ߌࠆ TC, LDL-C, non-HDL-C ߩᐔဋ୯ߩᏅߪ‫ోࠇߙࠇߘޔ‬૕ߢ᦭ᗧ
ߢ޽ߞߚ‫ޔߒ߆ߒޕ‬੤⛊‫ۀ‬࿃ࠍ‫ގ‬ᢛߒߚᐔဋ୯ߩᏅߢߪ LDL-C ߩߺ᦭ᗧ(p=0.04)ߢ޽
ࠅ‫ޔ‬TC ߣ non-HDL-C ߢߪ᦭ᗧ௑ะߢ޽ߞߚ(ߘࠇߙࠇ p=0.06, p=0.06)‫ޕ‬
ProPro ߦኻߔࠆ Leu ߦ߅ߌࠆᄙᄌ୲ࠍ‫ގ‬ᢛߒߚ TC ဎ୯, LDL-C ဎ୯, non-HDL-C ဎ
୯ߩ ORs ߪߘࠇߙࠇ‫ޔ‬1.11 (95%CI; 1.01–1.23), 1.11 (95%CI; 1.00–1.23), 1.16 (95%CI;
1.03–1.30)ߢ޽ߞߚ‫ޕ‬ห᭽ߩ TG ဎ୯ߩ ORs ߪᒝ޿୲෻ᔕലᨐ߇‫ޔࠇࠄۇ‬LeuLeu ߢ 1.51
(95%CI; 1.03-2.20)ߢ޽ߞߚ‫ޕ‬ƭࢠඐਅ೷᦯↪Ě 443 ฬࠍචᄖߒ‫ޔ‬ห᭽ߩ۳ᨆࠍ؅ߞߚ
႐วߢ߽᦭ᗧᕈࠍ⛽ᜬߒߚ߇‫ޔ‬Leu ߦ߅ߌࠆ LDL-C ဎ୯ߩ OR ߩߺ᦭ᗧ௑ะߣߥߞߚ
(OR=1.09, 95%CI; 0.97–1.21)‫ ᧄޕ‬SNP ߩࡅ࠻‫׺‬ᷡƭࢠߦኻߔࠆᓇະߪ‫ޔ‬༦ଜ࡮༛ᾍü
ᘠߦࠃߞߡᄌൻߒߥ߆ߞߚ‫ޕ‬
‫ޣ‬Ęኤ‫ޤ‬
޿ߊߟ߆ߩᄢ‫ۉ‬ᮨࠦ࡯ࡎ࡯࠻⎇ⓥߦࠃߞߡ‫ޔ‬ƭࢠ⇣Ᏹ∝ߪ↢ᵴüᘠߛߌߢߥߊ‫ޔ‬ઞ
વ⊛‫ۀ‬࿃ߢ 40ޯ70%߇‫ށ‬᣿ߢ߈ࠆߣႎ๔ߐࠇߡ߅ࠅ‫⎇ᧄޔ‬ⓥߦࠃߞߡ߽ߘߩ৻┵߇␜
ໂߐࠇߚ‫ ᧄߢ߹ࠇߎޕ‬SNP ߇ࡅ࠻‫׺‬ᷡƭࢠỚᐲߣീਗ਼ߔࠆߣ޿߁ႎ๔ߪߥ޿߇‫⎇ᧄޔ‬
ⓥߪಽሶ↢‛ቇ⎇ⓥߩᚑᨐߦၮߠ޿ߚត⚝⊛ᮮᢿ⎇ⓥߢ޽ࠆ‫ޕ‬෶‫ࡓࡁࠥోޔ‬ീਗ਼۳ᨆ
ߪࡅ࠻‫׺‬ᷡƭࢠỚᐲߦീଥߔࠆ SNPs ࠍᄙᢙႎ๔ߒߡ߅ࠅ‫ޔ‬ApoE ઞવሶᄙဳߥߤߩᓇ
ະ߇ᭂ߼ߡᒝ޿ SNPs ࠍචߌ߫‫ᧄޔ‬ᄙဳߥߤߩ SNP ৻ߟ޽ߚࠅߩലᨐߪᲧফ⊛ዊߐ޿‫ޕ‬
༙↢ᵴ߿ॺ૕ᵴേ୲ߥߤࠍĘᘦߒߡ޿ߥ޿ߎߣ߇ᧄ⎇ⓥߩඒ⇇ߩ৻ߟߣߒߡ᜼ߍࠄࠇ
ࠆ‫ޕ‬෶‫⎇ᧄޔ‬ⓥߪត⚝⊛⎇ⓥߢ޽ࠆߎߣ߆ࠄᄙ୰Ყফᬌቯߩߚ߼ߩࡏࡦࡈࠚࡠ࡯࠾ߩ
ٜᱜࠍ؅ߞߡ޿ߥ޿‫ޕ‬
‫ޤݶ⚿ޣ‬
ᧄ⎇ⓥߪ‫ޔ‬uPA ઞવሶᄙဳߩ PLAU Pro141Leu ߇ࡅ࠻‫׺‬ᷡƭࢠỚᐲߦᓇະࠍਈ߃ࠆ
‫ۀ‬࿃ߩ৻ߟߢ޽ࠆ੐ࠍ␜ໂߒߚ‫੹ޕ‬ᓟ‫ઁޔ‬෨࿅ߢߩౣ⃻ᕈߩ‫ܭ‬᣿߅ࠃ߮ઞવሶശ੤੕
૞↪ߥߤࠍĘᘦߒߚ⎇ⓥ߇᳞߼ࠄࠇࠆ‫ޕ‬
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施設内感染を起こす緑膿菌の水系環境における生息実態と病原性保有の

平成 20 年度酸性降下物量調査結果

タイムスケジュール