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2011 Fiscal Year Annual Research Report

脂質メディエーター関連遺伝子のSNPと疾患

Planned Research

Project AreaMachineries of bioactive lipids in homeostasis and diseases
Project/Area Number 22116010
Research InstitutionKyushu University

Principal Investigator

清原 裕  九州大学, 医学研究院, 教授 (80161602)

Co-Investigator(Kenkyū-buntansha) 久保 充明  独立行政法人理化学研究所, 横浜研究所・ゲノム医科学研究センター, 副センター長 (30442958)
Keywords脂肪酸分面 / エイコサペンタエン酸 / アラキドン酸 / エイコサセン酸 / 追跡調査 / 虚血性心疾患 / 肥満 / メタボリックシンドローム
Research Abstract

1.血L中脂肪酸の疫学(清原):(1)血清エイコサペンタエン酸(EPA)/アラキドン酸(AA)比と心血管病発症の関連を検討した。2002年の福岡県久山町の循環器健診を受診した心血管病の既往歴のない40歳以上の一般住民3,003名を5年間前向きに追跡した。追跡期間に191人が死亡し、127人が心血管病を発症した。血清EPA/AA比のレベルを0.25未満、0.25-049、0.50-0.74、0.75以上の4分位で4群に分けた。対象者におけるEPA/AA比の中央値は0.41(四分位範囲0.29-0.59)であった。EPA/AA比が0.75以上、0.50-0.74、0.25-0.49、0.25未満と低下するに伴い、性・年齢調整後の総死亡率(対千人年)は11.5、12.8、11.8、23.5と有意に上昇した(p=0.01)。さらにEPA/AA比と心血管病発症の関係を検討すると、集団全体では有意な関連を認めなかった。そこで、血清高感度C反応性蛋白(hs-CRP)値のレベル別に解析したところ、hs-CRP1.0mg/L以上の群において、EPA/AA比と心血管病の発症リスクの間には有意な負の直線関係を認めた(p=0.02)。この群における心血管病発症の相対危険(多変量調整)は、EPA/AA比が0.25低下する毎に1.66倍(95%CI 1.14-2.42)有意に上昇した。一方、hs-CRP1.0mg/L未満の群では、EPA/AA比と心血管病発症との間に有意な関連は認めなかった。
(2)2002年に空腹で健診を受診した40歳以上の住民3,210名を対象として、エイコセン酸の血清脂肪酸分画に占める割合を重量%で求めた。エイコセン酸割合を0.13未満、0.14-0.16、0.17-0.20、0.21以上の4分位の4群に分類した。エイコセン酸割合と肥満・インスリン抵抗性の関連をみると、4分位のレベルが上昇すると、BMI、HOMA-IR、腹囲、hs-CRPの値、肥満およびメタボリックシンドロームの割合が有意に低下した(p<0.05)。
2.脂質メディエーター関連遺伝子群のSNPs測定(久保):脂質メディエーターの関連遺伝子群118SNPsを選び、2002年に健診を受診した3,196名に対してSNPタイピングを行い、データベース化した。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

ヒト血中における脂肪酸分画を測定し、追跡研究において血清エイコサペンタエン酸(EPA)/アラキドン酸(AA)比と心血管病発症との関連を明らかにした。脂質メディエーター関連遺伝子群のSNP測定も順調に進み、解析が行われようとしている。

Strategy for Future Research Activity

疫学研究において、脂肪酸分画と心血管病およびその危険因子との関係を明らかにしていく。また、脂質メディエーター関連遺伝子群のSNPと疾患との関連について解析を行う。研究の遂行上、とくに問題点はない。

  • Research Products

    (48 results)

All 2012 2011

All Journal Article (33 results) (of which Peer Reviewed: 32 results) Presentation (11 results) Book (4 results)

  • [Journal Article] Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations2012

    • Author(s)
      Okada Y. et. al.
    • Journal Title

      Nat Genet

      Volume: 44 Pages: 302-306

    • DOI

      10.1038/ng.1086

  • [Journal Article] A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese2012

    • Author(s)
      Okada, Y., et.al.
    • Journal Title

      PLoS Genet

      Volume: 8(1) Pages: e1002455

    • DOI

      10.1371/journal.pgen.1002455 PGENETICS-D-11-01026[pii]

    • Peer Reviewed
  • [Journal Article] Development and function of invariant natural killer T cells producing t(h) 2- and t(h) 17-cytokines2012

    • Author(s)
      Watarai, H., et.al.
    • Journal Title

      PLoS Biol

      Volume: 10(2) Pages: e1001255

    • DOI

      10.1371/journal.pbio.1001255 PBIOLOGY-D-11-02362[pii]

    • Peer Reviewed
  • [Journal Article] Role of mast cells and basophils in IgE responses and in allergic airway hyperrpsponsiveness2012

    • Author(s)
      Sawaguchi, M., et.al.
    • Journal Title

      J Immunol

      Volume: 188(4) Pages: 1809-18

    • DOI

      jimmunol.1101746[pii] 10.4049/jimmunol.1101746

    • Peer Reviewed
  • [Journal Article] Dose-adjustment study of tamoxifen based on CYP2D6 genotypes in Japanese breast cancer patients2012

    • Author(s)
      Kiyotani, K., et.al.
    • Journal Title

      Breast Cancer Res Treat

      Volume: 131(1) Pages: 137-45

    • DOI

      10.1007/s10549-011-1777-7

    • Peer Reviewed
  • [Journal Article] N-terminal pro-brain natriuretic peptide and risk of cardiovascular events in a Japanese community : the Hisayama Study2011

    • Author(s)
      Doi, Y., et.al.
    • Journal Title

      Arterioscler Thromb Vase Biol

      Volume: 31(12) Pages: 2997-3003

    • DOI

      ATVBAHA.111.223669[pii] 10.1161/ATVBAHA.111.223669

    • Peer Reviewed
  • [Journal Article] Combined effects of smoking and hypercholesterolemia on the risk of stroke and coronary heart disease in Japanese : the Hisayama Study2011

    • Author(s)
      Hata, J., et.al.
    • Journal Title

      Cerebrovasc Dis

      Volume: 31(5) Pages: 477-84

    • DOI

      000324392[pii] 10.1159/000324392

    • Peer Reviewed
  • [Journal Article] Association of Alzheimer disease pathology with abnormal lipid metabolism : the Hisayama Study2011

    • Author(s)
      Matsuzaki, T., et.al.
    • Journal Title

      Neurology

      Volume: 77(11) Pages: 1068-75

    • DOI

      77/11/1068[pii] 10.1212/WNL.0b013e31822e145d

    • Peer Reviewed
  • [Journal Article] Glucose tolerance status and risk of dementia in the community : the Hisayama Study2011

    • Author(s)
      Ohara, T., et.al.
    • Journal Title

      Neurology

      Volume: 77(12) Pages: 1126-34

    • DOI

      77/12/1126[pii] 10.1212/WNL.0b013e31822f0435

    • Peer Reviewed
  • [Journal Article] Apolipoprotein genotype for prediction of Alzheimer's disease in older Japanese : the Hisayama Study2011

    • Author(s)
      Ohara, T., et.al.
    • Journal Title

      J Am Geriatr Soc

      Volume: 59(6) Pages: 1074-9

    • DOI

      10.1111/j.1532-5415.2011.03405.x

    • Peer Reviewed
  • [Journal Article] Albuminuria as a risk factor for peripheral arterial disease in a general population: the Hisayama Study2011

    • Author(s)
      Usui, T., et.al.
    • Journal Title

      J Atheroscler Thromb

      Volume: 18(8) Pages: 705-12

    • DOI

      JST.JSTAGE/jat/7682[pii]

    • Peer Reviewed
  • [Journal Article] White blood cell count and risk of gastric cancer incidence in a general Japanese population : the Hisayama Study2011

    • Author(s)
      Iida, M., et.al.
    • Journal Title

      Am J Epidemiol

      Volume: 175(6) Pages: 504-10

    • DOI

      kwr345[pii] 10.1093/aje/kwr345

    • Peer Reviewed
  • [Journal Article] Effectiveness of the salivary occult blood test as a screening method for periodontal status2011

    • Author(s)
      Shimazaki, Y., et.al.
    • Journal Title

      J Periodontol

      Volume: 82(4) Pages: 581-7

    • DOI

      10.1902/jop.2010.100304

    • Peer Reviewed
  • [Journal Article] Nine-year incidence and risk factors for retinal vein occlusion in a general Japanese population : the Hisayama Study2011

    • Author(s)
      Arakawa, S., et.al.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 52(8) Pages: 5905-9

    • DOI

      iovs.11-7775[pii] 10.1167/iovs.11-7775

    • Peer Reviewed
  • [Journal Article] High serum bilirubin levels and diabetic retinopathy : the Hisayama Study2011

    • Author(s)
      Yasuda, M., et.al.
    • Journal Title

      Ophthalmology

      Volume: 118(7) Pages: 1423-8

    • DOI

      S0161-6420(10)01302-3[pii] 10.1016/j.ophtha.2010.12.009

    • Peer Reviewed
  • [Journal Article] Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese2011

    • Author(s)
      Kou, I., et.al.
    • Journal Title

      PLoS One

      Volume: 6(5) Pages: e19641

    • DOI

      10.1371/journal.pone.0019641 PONE-D-10-06247[pii]

    • Peer Reviewed
  • [Journal Article] Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis : case-control studies2011

    • Author(s)
      Hirota, T., et.al.
    • Journal Title

      PLoS One

      Volume: 6(11) Pages: e26987

    • DOI

      10.1371/journal.pone.0026987 PONE-D-11-14805[pii]

    • Peer Reviewed
  • [Journal Article] Identification of nine novel loci associated with white blood cell subtypes in a Japanese population2011

    • Author(s)
      Okada, Y., et.al.
    • Journal Title

      PLoS Genet

      Volume: 7(6) Pages: e1002067

    • DOI

      10.1371/journal.pgen.1002067 PGENETICS-D-10-00263[pii]

    • Peer Reviewed
  • [Journal Article] Multiple loci are associated with white blood cell phenotypes2011

    • Author(s)
      Nalls, M.A., et.al.
    • Journal Title

      PLoS Genet

      Volume: 7(6) Pages: e1002113

    • DOI

      10.1371/journal.pgen.1002113 PGENETICS-D-10-00114[pii]

    • Peer Reviewed
  • [Journal Article] The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells2011

    • Author(s)
      Motomura, Y., et.al.
    • Journal Title

      Nat Immunol

      Volume: 12(5) Pages: 450-9

    • DOI

      ni.2020[pii] 10.1038/ni.2020

    • Peer Reviewed
  • [Journal Article] A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis2011

    • Author(s)
      Takahashi, Y., et.al.
    • Journal Title

      Nat Genet

      Volume: 43(12) Pages: 1237-40

    • DOI

      ng.974[pii] 10.1038/ng.974

    • Peer Reviewed
  • [Journal Article] Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers2011

    • Author(s)
      Miki, D., et.al.
    • Journal Title

      Nat Genet

      Volume: 43(8) Pages: 797-800

    • DOI

      ng.876[pii] 10.1038/ng.876

    • Peer Reviewed
  • [Journal Article] Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population2011

    • Author(s)
      Hirota, T., et.al.
    • Journal Title

      Nat Genet

      Volume: 43(9) Pages: 893-6

    • DOI

      ng.887[pii] 10.1038/ng.887

    • Peer Reviewed
  • [Journal Article] Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population2011

    • Author(s)
      Arakawa, S., et.al.
    • Journal Title

      Nat Genet

      Volume: 43(10) Pages: 1001-4

    • DOI

      ng.938[pii] 10.1038/ng.938

    • Peer Reviewed
  • [Journal Article] Inverse association of IL28B genotype and liver mRNA expression of genes promoting or suppressing antiviral state2011

    • Author(s)
      Abe, H., et.al.
    • Journal Title

      J Med Virol

      Volume: 83(9) Pages: 1597-607

    • DOI

      10.1002/jmv.22158

    • Peer Reviewed
  • [Journal Article] IL28 variation affects expression of interferon stimulated genes and peg-interferon and ribavirin therapy2011

    • Author(s)
      Abe, H., et.al.
    • Journal Title

      J Hepatol

      Volume: 54(6) Pages: 1094-101

    • DOI

      S0168-8278(10)00914-1[pii] 10.1016/j.jhep.2010.09.019

    • Peer Reviewed
  • [Journal Article] IL-28B predicts response to chronic hepatitis C therapy-fine-mapping and replication study in Asian populations2011

    • Author(s)
      Ochi, H., et.al.
    • Journal Title

      J Gen Virol

      Volume: 92(5) Pages: 1071-81

    • DOI

      vir.0.029124-0[pii] 10.1099/vir.0.029124-0

    • Peer Reviewed
  • [Journal Article] Meta-analysis of published studies identified eight additional common susceptibility loci for Crohn's disease and ulcerative colitis2011

    • Author(s)
      Umeno, J., et.al.
    • Journal Title

      Inflamm Bowel Dis

      Volume: 17(12) Pages: 2407-15

    • DOI

      10.1002/ibd.21651

    • Peer Reviewed
  • [Journal Article] Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population2011

    • Author(s)
      Ozeki, T., et.al.
    • Journal Title

      Hum Mol Genet

      Volume: 20(5) Pages: 1034-41

    • DOI

      ddq537[pii] 10.1093/hmg/ddq537

    • Peer Reviewed
  • [Journal Article] Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus2011

    • Author(s)
      Okada, Y., et.al.
    • Journal Title

      Hum Mol Genet

      Volume: 20(6) Pages: 1224-31

    • DOI

      ddq551[pii] 10.1093/hmg/ddq551

    • Peer Reviewed
  • [Journal Article] A functional variant in ZNF512B is associated with susceptibility to amyotrophic lateral sclerosis in Japanese2011

    • Author(s)
      Iida, A., et.al.
    • Journal Title

      Hum Mol Genet

      Volume: 20(18) Pages: 3684-92

    • DOI

      ddr268[pii] 10.1093/hmg/ddr268

    • Peer Reviewed
  • [Journal Article] PlatinumCNV : a Bayesian Gaussian mixture model for genotyping copy number polymorphisms using SNP array signal intensity data2011

    • Author(s)
      Kumasaka, N., et.al.
    • Journal Title

      Genet Epidemiol

      Volume: 35(8) Pages: 831-44

    • DOI

      10.1002/gepi.20633

    • Peer Reviewed
  • [Journal Article] Genome-wide association study on bipolar disorder in the Bulgarian population2011

    • Author(s)
      Yosifova, A., et.al.
    • Journal Title

      Genes Brain Behav

      Volume: 10(7) Pages: 789-97

    • DOI

      10.1111/j.1601-183X.2011.00721.x

    • Peer Reviewed
  • [Presentation] 生活習慣病の危険因子:久山町研究2011

    • Author(s)
      清原裕
    • Organizer
      第18回日本未病システム学会学術総会
    • Place of Presentation
      名古屋市(招待講演)
    • Year and Date
      2011-11-19
  • [Presentation] 糖尿病と認知症の疫学:久山町研究2011

    • Author(s)
      清原裕
    • Organizer
      第30回日本認知症学会学術集会
    • Place of Presentation
      東京都(招待講演)
    • Year and Date
      2011-11-11
  • [Presentation] 高血圧とメタボリックシンドロームの疫学2011

    • Author(s)
      清原裕
    • Organizer
      第34回日本高血圧学会総会
    • Place of Presentation
      宇都宮市(招待講演)
    • Year and Date
      2011-10-21
  • [Presentation] 変貌する日本人の生活習慣病の現状と課題:久山町研究2011

    • Author(s)
      清原裕
    • Organizer
      第61回日本体質医学会総会
    • Place of Presentation
      東京都(招待講演)
    • Year and Date
      2011-10-08
  • [Presentation] 日本人におけるエビデンス構築の意義:Hisayama Studyを通して2011

    • Author(s)
      清原裕
    • Organizer
      第54回日本歯周病学会秋季学術大会
    • Place of Presentation
      下関市(招待講演)
    • Year and Date
      2011-09-15
  • [Presentation] Secular trends in hypertension and risk of stroke : the Hisayama Study2011

    • Author(s)
      Kiyohara Y
    • Organizer
      第43回日本動脈硬化学会総会
    • Place of Presentation
      札幌市(招待講演)
    • Year and Date
      2011-07-15
  • [Presentation] 高齢者における脳血管疾患を考慮した脂質管理2011

    • Author(s)
      清原裕
    • Organizer
      第27回日本老年学会総会
    • Place of Presentation
      東京都(招待講演)
    • Year and Date
      2011-06-16
  • [Presentation] 変貌する心血管病の現状と課題:久山町研究2011

    • Author(s)
      清原裕
    • Organizer
      第47回日本循環器病予防学会・日本循環器管理研究協議会総会
    • Place of Presentation
      福岡市(招待講演)
    • Year and Date
      2011-06-03
  • [Presentation] 認知症のコホート研究:久山町研究2011

    • Author(s)
      清原裕
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋市(招待講演)
    • Year and Date
      2011-05-19
  • [Presentation] コホート研究の実践:久山町研究2011

    • Author(s)
      清原裕
    • Organizer
      第39回日本血管外科学会学術総会
    • Place of Presentation
      沖縄県宜野湾市(招待講演)
    • Year and Date
      2011-04-21
  • [Presentation] 日本人の心血管病のリスクを考える:久山町研究2011

    • Author(s)
      清原裕
    • Organizer
      第39回日本血管外科学会学術総会
    • Place of Presentation
      沖縄県宜野湾市(招待講演)
    • Year and Date
      2011-04-21
  • [Book] Visual糖尿病臨床のすべて2011

    • Author(s)
      平川洋一郎, 他
    • Total Pages
      133-140
    • Publisher
      中山書店
  • [Book] 糖尿病学20112011

    • Author(s)
      向井直子, 他
    • Total Pages
      128-133
    • Publisher
      診断と治療社
  • [Book] 高血圧ナビゲーター2011

    • Author(s)
      清原裕, 他
    • Total Pages
      50-51
    • Publisher
      メディカルレビュー社
  • [Book] すべてがわかる最新糖尿病2011

    • Author(s)
      清原裕, 他
    • Total Pages
      254-258
    • Publisher
      照林社

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Published: 2013-06-26  

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