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2010 Fiscal Year Final Research Report

Identification and a functional analysis of susceptibility genes of Eating Disorders by GWAS

Research Project

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Project/Area Number 20390201
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

KOMAKI Gen  National Center of Neurology and Psychiatry, 精神保健研究所心身医学研究部, 部長 (70225564)

Co-Investigator(Kenkyū-buntansha) ANDO Tetsuya  (独)国立精神・神経医療研究センター, 精神保健研究所心身医学研究部, 室長 (50311428)
INOKO Hidetoshi  東海大学, 大学院・分子生命科学, 教授 (10101932)
Co-Investigator(Renkei-kenkyūsha) NAKABAYASHI Kazuhiko  国立成育医療センター研究所, 周産期病態研究部, 室長 (10415557)
Project Period (FY) 2008 – 2010
Keywords心療内科学
Research Abstract

In the present study, we examined microsatellite markers that had been already detected in 10regions in Anorexia Nervosa patient samples in the previous study. As a result, only one locus, D1S0562i, was identified where the allele and frequency were identical to the previous one and this finding was satisfied with the Hardy-Weinberg Equilibrium. Finally, two haplotypes were estimated that are higher in odds ratio than that of D1S0562i alone.

  • Research Products

    (66 results)

All 2011 2010 2009 2008 Other

All Journal Article (40 results) (of which Peer Reviewed: 32 results) Presentation (20 results) Book (3 results) Remarks (3 results)

  • [Journal Article] Functional polymorphism in the GPR55 gene is associated with anorexia nervosa.2011

    • Author(s)
      Ishiguro H, Onaivi ES, Horiuchi Y, Imai K, Komaki G, Ishikawa T, Suzuki M, Watanabe Y, Ando T, Higuchi S, Arinami T
    • Journal Title

      Synapse. 65(2)

      Pages: 103-8, doi:10.1002/syn.20821

    • Peer Reviewed
  • [Journal Article] The reliability and validity of the Japanese version of the Levels of Emotional Awareness Scale (LEAS-J).2011

    • Author(s)
      Igarashi T, Komaki G, Lane RD, Moriguchi Y, Nishimura H, Arakawa H, Gondo M, Terasawa Y, Sullivan CV, Maeda M
    • Journal Title

      Biopsychosoc Med. 5(1)

      Pages: 2

    • Peer Reviewed
  • [Journal Article] Japanese Genetic Research Group for Eating Disorders. A ghrelin gene variant may predict crossover rate from restricting-type anorexia nervosa to other phenotypes of eating disorders : a retrospective survival analysis.2010

    • Author(s)
      Ando T, Komaki G, Nishimura H, Naruo T, Okabe K, Kawai K, Takii M, Oka T, Kodama N, Nakamoto C, Ishikawa T, Suzuki-Hotta M, Minatozaki K, Yamaguchi C, Nishizono-Maher A, Kono M, Kajiwara S, Suematsu H, Tomita Y, Ebana S, Okamoto Y, Nagata K, Nakai Y, Koide M, Kobayashi N, Kurokawa N, Nagata T, Kiriike N, Takenaka Y, Nagamine K, Ookuma K, Murata S
    • Journal Title

      Psychiatr Genet. 20(4)

      Pages: 153-9

    • Peer Reviewed
  • [Journal Article] Association of toll-like receptor 2 gene polymorphisms with normal tension glaucoma.2010

    • Author(s)
      Nakamura J, Meguro A, Ota M, Nomura E, Nishide T, Kashiwagi K, Inoko H, Mizuki N, et al
    • Journal Title

      Mol Vis 15

      Pages: 2905-2910

    • Peer Reviewed
  • [Journal Article] Polymorphic SVAretrotransposons at four loci and their association with classical HLA class I alleles in Japanese, Caucasians and African Americans.2010

    • Author(s)
      Kohno T, Kunitoh H, Shimada Y, Kulski JK, Shigenari A, Inoko H
    • Journal Title

      Immunogenetics 62

      Pages: 211-230

    • Peer Reviewed
  • [Journal Article] Polymorphic major histocompatibility complex class II Alu insertions at five loci and their association with HLA-DRB1 and -DQB1 in Japanese and Caucasians.2010

    • Author(s)
      Kulski JK, Shigenari A, Shiina T, Inoko H
    • Journal Title

      Tissue Antgens 76

      Pages: 35-47

    • Peer Reviewed
  • [Journal Article] Flow cytometric identification of CD93 expression on naive T lymphocytes (CD4(+)CD45RA(+) cells) in human neonatal umbilical cord blood.2010

    • Author(s)
      Ikewaki N, Yamao H, Kulski JK, Inoko H
    • Journal Title

      J Clin Immunol 30

      Pages: 723-733

    • Peer Reviewed
  • [Journal Article] Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behcet's disease susceptibility loci.2010

    • Author(s)
      Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, Song YW, Lee EB, Kitaichi N, Namba K, Horie Y, Takeno M, Sugita S, Mochizuki M, Bahram S, Ishigatsubo Y, Inoko H
    • Journal Title

      Nature Genet 42

      Pages: 703-706

    • Peer Reviewed
  • [Journal Article] Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.2010

    • Author(s)
      Michikawa Y, Suga T, Ishikawa A, Hayashi H, Oka A, Inoko H, Iwakawa M, Imai T
    • Journal Title

      BMC Med Genet 11

      Pages: 123

    • Peer Reviewed
  • [Journal Article] TRIM39 and RNF39 are associated with Behcet's disease independently of HLA-B*51 and -A*26.2010

    • Author(s)
      Kurata R, Nakaoka H, Tajima A, Hosomichi K, Shiina T, Meguro A, Mizuki N, Ohono S, Inoue I, Inoko H
    • Journal Title

      Biochem Biophys Res Commun 401

      Pages: 533-535

    • Peer Reviewed
  • [Journal Article] Which CIDE are you on? Apoptosis and energy metabolism.2010

    • Author(s)
      Yonezawa T, Kurata R, Kimura M, Inoko H
    • Journal Title

      Mol Biosyst

    • Peer Reviewed
  • [Journal Article] Genotyping HLA-DRB1 and HLA-DQB1 alleles in Japanese patients with normal tension glaucoma.2010

    • Author(s)
      Suzuki M, Meguro A, Ota M, Nomura E, Kato T, Nomura N, Kashiwagi K, Mabuchi F, Inoko H, et al
    • Journal Title

      Mol Vis 16

      Pages: 1874-1879

    • Peer Reviewed
  • [Journal Article] 【最近のGWAS研究の成果】神経性食欲不振症のゲノムワイド関連研究2010

    • Author(s)
      中林一彦,小牧元,白澤専二
    • Journal Title

      BIO Clinica 25(6)

      Pages: 494-499

  • [Journal Article] The Human Mirror Neuron System in a Population With Deficient Self-Awareness : An fMRI Study in Alexithymia.2009

    • Author(s)
      Moriguchi Y, Ohnishi T, Decety J, Hirakata M, Maeda M, Matsuda H, Komaki G
    • Journal Title

      Human Brain Mapping 30(7)

      Pages: 2063-76

    • Peer Reviewed
  • [Journal Article] Prospects of psychosomatic medicine.2009

    • Author(s)
      Komaki G, Moriguchi Y, Ando T, Yoshiuchi K, Nakao M
    • Journal Title

      Biopsychosoc Med. 3

      Pages: 1

    • Peer Reviewed
  • [Journal Article] Japanese Genetic Research Group for Eating Disorders (JGRED), Shirasawa S.Identification of novel candidate loci for anorexia nervosa at 1q41 and 11q22 in Japanese by a genome-wide association analysis with microsatellite markers.2009

    • Author(s)
      Nakabayashi K, Komaki G, Tajima A, Ando T, Ishikawa M, Nomoto J, Hata K, Oka A, Inoko H, Sasazuki T
    • Journal Title

      J Hum Genet.(Epub) 54(9)

      Pages: 531-7

    • Peer Reviewed
  • [Journal Article] Validity issues in the assessment of alexithymia related to the developmental stages of emotional cognition and language.2009

    • Author(s)
      Nishimura H, Komaki G, Igarashi T, Moriguchi Y, Kajiwara S, Akasaka T
    • Journal Title

      Biopsychosoc Med. 3

      Pages: 12

    • Peer Reviewed
  • [Journal Article] Detecting linkage between a trait and a marker in a random mating population without pedigree record.2009

    • Author(s)
      Mano S, Endo TA, Oka A, Ozawa A, Gojobori T, Inoko H
    • Journal Title

      PLoS ONE 4

      Pages: e4956

    • Peer Reviewed
  • [Journal Article] Recombinant DNA technologies for construction of precisely designed transgene constructs.2009

    • Author(s)
      Ohtsuka M, Kimura M, Tanaka M, Inoko H
    • Journal Title

      Curr Pharm Biotechnol 10

      Pages: 244-251

    • Peer Reviewed
  • [Journal Article] PKC Delta and Epsilon in drug targeting and therapeutics.2009

    • Author(s)
      Yonezawa T, Kurata R, Kimura M, Inoko H
    • Journal Title

      Recent Patents on DNA & Gene Sequences. 3

      Pages: 96-101

    • Peer Reviewed
  • [Journal Article] Assessment of chromosome 19 for genetic association in severe chronic periodontitis.2009

    • Author(s)
      Tabeta K, Shimada Y, Tai H, Ishihara Y, Noguchi T, Inoko H, et al
    • Journal Title

      J Periodontol 80

      Pages: 663-671

    • Peer Reviewed
  • [Journal Article] Polymorphisms of NKG2D ligands : diverse RAET1/ULBP genes in northeastern Thais.2009

    • Author(s)
      Romphruk AV, Romphruk A, Naruse TK, Raroengjai S, Puapairoj C, Inoko H, Leelayuwat C
    • Journal Title

      Immunogenetics 61

      Pages: 611-617

    • Peer Reviewed
  • [Journal Article] Genetics of Behcet's disease inside and outside the MHC.2009

    • Author(s)
      Meguro A, Inoko H, Ota M, Katsuyama Y, Oka A, Okada E, Yamakawa R, Yuasa T, Fujioka T, Ohno S, Bahram S, Mizuki N
    • Journal Title

      Ann Rheum Dis

    • Peer Reviewed
  • [Journal Article] Nutritional and hormonal regulation of uncoupling protein 2.2009

    • Author(s)
      Yonezawa T, Kurata R, Hosomichi K, Kono A, Kimura M, Inoko H
    • Journal Title

      IUBMB Life 61

      Pages: 1123-1131

    • Peer Reviewed
  • [Journal Article] 摂食障害の遺伝子研究-候補遺伝子法から全ゲノム相関解析へ-2009

    • Author(s)
      安藤哲也,小牧元
    • Journal Title

      心身医学 49(1)

      Pages: 47-56

  • [Journal Article] 摂食障害研究の最前線摂食障害の遺伝子研究候補遺伝子法から全ゲノム相関解析へ2009

    • Author(s)
      安藤哲也,小牧元
    • Journal Title

      心身医学 49(1)

      Pages: 47-56

  • [Journal Article] 女性の食行動の異常,摂食障害と環境・遺伝要因2009

    • Author(s)
      安藤哲也
    • Journal Title

      臨床環境医学 18(2)

      Pages: 83-90

  • [Journal Article] 日本人の摂食障害姉妹発症例における生涯病型、代償行動、ならびに体重の関連性の有無について2009

    • Author(s)
      後藤直子,小牧元,安藤哲也,伊澤敏,石川俊男,大隈和喜,岡部憲二郎,黒川順夫,小西貴幸,高宮静男,武井美智子,傳田健三,冨田和己,長井信篤,長峯清英,西園マーハ文,本間一正,町田英世
    • Journal Title

      心身医学(第24回2010年日本心身医学会石川記念賞受賞論文) Vol.49, No.5

      Pages: 373-380

    • Peer Reviewed
  • [Journal Article] 乾癬のマイクロサテライトによるゲノムワイド関連解析2009

    • Author(s)
      岡晃、猪子英俊
    • Journal Title

      実験医学 27

      Pages: 80-85

  • [Journal Article] Japanese Genetic Research Group for Eating Disorders : Psychological and weight-related characteristics of patients with anorexia nervosa-restricting type who later develop bulimia nervosa.2008

    • Author(s)
      Nishimura H, Komaki G, Ando T, Nakahara T, Oka T, Kawai K, Nagata T, Nishizono A, Okamoto Y, Okabe K, Koide M, Yamaguchi C, Saito S, Ohkuma K, Nagata K, Naruo T, Takii M, Kiriike N, Ishikawa T
    • Journal Title

      BioPsychoSocial Medicine 2:5

      Pages: doi:10.1186/1751-0759-2-5

    • Peer Reviewed
  • [Journal Article] A genome-wide association scan for asthma in a general Australian population.2008

    • Author(s)
      Hui J, Oka A, James A, Palmer LJ, Musk AW, Beilby J, Inoko H
    • Journal Title

      Hum Genet 123

      Pages: 297-306

    • Peer Reviewed
  • [Journal Article] Association of the toll-like receptor 4 gene polymorphisms with Behcet's disease.2008

    • Author(s)
      Meguro A, Ota M, Katsuyama Y, Oka A, Ohno S, Inoko H, Mizuki N
    • Journal Title

      Ann Rheum 67

      Pages: 725-727

    • Peer Reviewed
  • [Journal Article] Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6.2008

    • Author(s)
      Ohtsuka M, Inoko H, Kulski JK, Yoshimura S
    • Journal Title

      BMC Genomics 9

      Pages: 178-192

    • Peer Reviewed
  • [Journal Article] Genome-wide association analysis with selective genotyping identifies candidate loci for adult height at 8q21.13 and 15q22.33-q23 in Mongolians.2008

    • Author(s)
      Kimura T, Kobayashi T, Munkhbat B, Oyungerel G, Bilegtsaikhan T, Anar D, Jambaldorj J, Munkhsaikhan S, Munkhtuvshin N, Hayashi H, Oka A, Inoue I, Inoko H
    • Journal Title

      Hum Genet 123

      Pages: 655-660

    • Peer Reviewed
  • [Journal Article] The amphioxus genome illuminates vertebrate origins and cephalochordate biology.2008

    • Author(s)
      Holland LZ, Albalat R, Azumi K, Benito-Gutierrez E, Blow MJ, Inoko H, et al
    • Journal Title

      Genome Res 18

      Pages: 11000-1111

    • Peer Reviewed
  • [Journal Article] Human endogenous retrovirus (HERVK9) structural polymorphism with haplotypic HLA-A allelic associations.2008

    • Author(s)
      Kulski JK, Shigenari A, Shiina S, Ota M, Hosomichi K, James I, Inoko H
    • Journal Title

      Genetics 108

      Pages: 446-457

    • Peer Reviewed
  • [Journal Article] Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma.2008

    • Author(s)
      Akiyama M, Yatsu K, Ota M, Katsuyama Y, Kashiwagi K, Inoko H, et al
    • Journal Title

      Br J Ophthalmol 192

      Pages: 1293-1296

    • Peer Reviewed
  • [Journal Article] 摂食障害の遺伝子2008

    • Author(s)
      安藤哲也,小牧元
    • Journal Title

      心療内科 12(4)

      Pages: 260-268

  • [Journal Article] 乾癬のマイクロサテライトによるゲノムワイド関連解析2008

    • Author(s)
      岡晃、猪子英俊
    • Journal Title

      医学のあゆみ 225

      Pages: 791-797

  • [Journal Article] 【摂食障害update】摂食障害の遺伝子2008

    • Author(s)
      安藤哲也,小牧元
    • Journal Title

      心療内科 12(4)

      Pages: 260-268

  • [Presentation] 若年女性の摂食障害傾向に影響する心理社会的ストレスとストレスコーピング2010

    • Author(s)
      安藤哲也,長谷川裕美,東風谷祐子,小林仁美,市丸雄平,小牧元
    • Organizer
      第15回日本心療内科学会総会・学術大会
    • Place of Presentation
      岡山
    • Year and Date
      20101120-20101121
  • [Presentation] 若年女性の摂食障害傾向と体型・体組成に対する心理社会的ストレスとストレスコーピングの影響2010

    • Author(s)
      安藤哲也,長谷川裕美,東風谷祐子,市丸雄平,小牧元
    • Organizer
      第26回日本ストレス学会学術総会
    • Place of Presentation
      福岡
    • Year and Date
      20101105-20101106
  • [Presentation] 摂食障害遺伝子解析研究協力者会議:脳由来神経栄養因子(BDNF)遺伝子Val66Met多型と神経性食欲不振症との関連の検討2010

    • Author(s)
      安藤哲也,石川俊男,鈴木(堀田)眞理,成尾鉄朗,岡部憲二郎,中原敏博,瀧井正人,河合啓介,米良貴嗣,中本智恵美,武井美智子,山口力,永田利彦,岡本百合,大隈和喜,小出将則,山中隆夫,村田志保,田村奈穂,切池信夫,市丸雄平,小牧元
    • Organizer
      第14回日本摂食障害学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20101002-20101003
  • [Presentation] Japanese Genetic Research Group For Eating Disorders (JGRED) : Genetic study for Japanese anorexia nervosa patients bygenome-wide association analysis with microsatellite markers.2010

    • Author(s)
      Komaki G, Nakabayashi K, Ando T, Inoko H, Shirasawa S
    • Organizer
      The 14th Congress of the Asian College of Psychosomatic Medicine
    • Place of Presentation
      Beijing,
    • Year and Date
      20100910-20100912
  • [Presentation] 中学生女子の摂食障害早期発見のためのスクリーニング調査2010

    • Author(s)
      小牧元,西村大樹,荒川裕美,前田基成
    • Organizer
      第51回日本心身医学会総会ならびに学術講演会
    • Place of Presentation
      仙台
    • Year and Date
      20100626-20100627
  • [Presentation] 若年女性のストレスコーピングと摂食障害傾向,体型,血清脂質との関連2010

    • Author(s)
      長谷川裕美,安藤哲也,市丸雄平,東風谷祐子,小牧元
    • Organizer
      第51回日本心身医学会総会ならびに学術講演会
    • Place of Presentation
      仙台
    • Year and Date
      20100626-20100627
  • [Presentation] Screening investigation for eating disorders among female juniorhigh students ; one year prospective study.2010

    • Author(s)
      Nishimura H, Komaki G, Arakawa H, Maeda M
    • Organizer
      International Conference on Eating Disorders
    • Place of Presentation
      Salzburg,
    • Year and Date
      20100610-20100612
  • [Presentation] Associations of stress coping styles with eating disorder-tendency and body composition in young Japanese women.2010

    • Author(s)
      Ando T, Hasegawa Y, Ichimaru Y, Komaki G
    • Organizer
      International Conference on Eating Disorders
    • Place of Presentation
      Salzburg
    • Year and Date
      20100610-20100612
  • [Presentation] 男子中学生の摂食障害傾向地域調査2010

    • Author(s)
      長谷部智子,西村大樹,東條光彦,立森久照,菊地裕絵,前田基成,小牧元
    • Organizer
      摂食障害学会
    • Place of Presentation
      東京
    • Year and Date
      2010-10-02
  • [Presentation] The Japanese Genetic Research Group For Eating Disorders : Role of ghrelin gene variants in eating disorders, and eating disorder-related characteristics of young Japanese women.2009

    • Author(s)
      Ando T, Komaki G, Ichimaru Y, Konjiki F
    • Organizer
      20^<th> World Congress on Psychosomatic Medicine, Turin
    • Place of Presentation
      Italy
    • Year and Date
      20090923-20090926
  • [Presentation] The relationship between the eating attitudes of college students and reasoning style and obsession.2009

    • Author(s)
      Arakawa H, Komaki G
    • Organizer
      20^<th> World Congress on Psychosomatic Medicine, Turin
    • Place of Presentation
      Italy
    • Year and Date
      20090923-20090926
  • [Presentation] 神経接着分子コンタクチン5遺伝子多型と若年女性の摂食障害傾向との関連2009

    • Author(s)
      安藤哲也,市丸雄平,近喰ふじ子,小牧元
    • Organizer
      第13回日本摂食障害学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20090912-20090913
  • [Presentation] 鼎談4病態生理2009

    • Author(s)
      小牧元
    • Organizer
      第13回日本摂食障害学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20090912-20090913
  • [Presentation] 若年者摂食障害早期発見・予防のためのスクリーニングを目的とする調査研究2009

    • Author(s)
      西村大樹,小牧元,荒川裕美,東條光彦,前田基成
    • Organizer
      第一回日本心身医学5学会合同集会(第50回日本心身医学会総会ならびに学術講演会)
    • Place of Presentation
      東京
    • Year and Date
      20090606-20090607
  • [Presentation] 神経接着分子contactin 5遺伝子の多型と若年女性の摂食障害関連特性の検討2009

    • Author(s)
      安藤哲也,市丸雄平,近喰ふじ子,小牧元
    • Organizer
      第一回日本心身医学5学会合同集会(第50回日本心身医学会総会ならびに学術講演会)
    • Place of Presentation
      東京
    • Year and Date
      20090606-20090607
  • [Presentation] 脳由来神経栄養因子(BDNF)遺伝子Val66Met多型と若年女性における摂食障害関連心理身体特性との関連2008

    • Author(s)
      安藤哲也,市丸雄平,近喰ふじ子,西村大樹,小牧元
    • Organizer
      第4回日本摂食障害学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20080920-20080921
  • [Presentation] Genetic study of eating disorders. Symposium4 : Biology of eating disorder2008

    • Author(s)
      小牧元, 安藤哲也
    • Organizer
      The 51^<st> Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      Toyama
    • Year and Date
      20080911-20080913
  • [Presentation] 若年女性における脳由来神経栄養因子(BDNF)遺伝子の変異と身体計測値および摂食障害関連心理特性との関連2008

    • Author(s)
      安藤哲也,近喰ふじ子,西村大樹,庄子雅保,小牧元
    • Organizer
      第49回日本心身医学会総会ならびに学術講演会
    • Place of Presentation
      札幌
    • Year and Date
      20080612-20080613
  • [Presentation] シンポジウムVI摂食障害の遺伝子研究-候補遺伝子法から全ゲノム相関解析へ2008

    • Author(s)
      安藤哲也,小牧元
    • Organizer
      第49回日本心身医学会総会ならびに学術講演会
    • Place of Presentation
      札幌
    • Year and Date
      20080612-20080613
  • [Presentation] 摂食障害とグレリン遺伝子多型2008

    • Author(s)
      安藤哲也
    • Organizer
      第8回グレリン研究会
    • Place of Presentation
      宮崎市
    • Year and Date
      2008-09-06
  • [Book] 医科栄養学(板倉弘重監修、近藤和雄・市丸雄平・佐藤和人編著)(摂食障害:神経性食欲不振症,神経性過食症)2010

    • Author(s)
      安藤哲也
    • Total Pages
      557-571
    • Publisher
      建帛社,東京
  • [Book] 症例に学ぶ用語集(監修日本心療内科学会編集日本心療内科学会用語委員会)(神経伝達物質(Neurotransmitter)心療内科実践ハンドブック)2009

    • Author(s)
      小牧元
    • Total Pages
      104-105
    • Publisher
      マイライフ社
  • [Book] 摂食障害救急患者治療マニュアル(日本摂食障害学会(編))(救急搬入時診察のポイント)2008

    • Author(s)
      小牧元
    • Publisher
      マイライフ社、東京
  • [Remarks] ホームページ等

  • [Remarks] 小牧元:摂食障害簡略版&詳細版.みんなのメンタルヘルス総合サイト~こころの病気・精神障害の方の治療・生活を応援する総合サイト

    • URL

      http://dev03.visual-l.com/portal/100625/disease/eat.html

  • [Remarks]

    • URL

      http://dev03.visual-l.com/portal/100625/disease_detail/1_04_02eat.html

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Published: 2012-01-26   Modified: 2016-04-21  

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