A functional analysis of novel obesity-related genes and a search for obesity-related genes

• Project/Area Number: 21591186
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kyoto University (2010-2011); The Institute of Physical and Chemical Research (2009)
• Principal Investigator: HOTTA Kikuko 京都大学, 医学研究科, 助教 (30360639)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肥満 / SCG3 / MTMR9 / SH2B1 / CYP17A1 / NT5C2 / MKKS / PNPLA1 / 内臓脂肪 / FTO / 肥満関連遺伝子 / 皮下脂肪 / 肥満症 / 非アルコール性脂肪肝炎 / 視床下部 / セクレトグラニン2 / セクレトグラニン3 / SEC16B

Research Abstract

We identified SCG2, which bound to SCG3 and facilitated the aggregation of NPY, orexin and MCH. We found that variations in the SEC16B, TMEM18, GNPDA2, BDNF, and FAIM2 genes were associated with obesity in the Japanese population. We also found that SNPs in the MKKS/BBS6, SCG3, MTMR9, and FTO genes were related to metabolic syndrome. We reported the association of FTO polymorphism with subcutaneous fat area and that of SH2B1 polymorphism with visceral fat area. The SNPs in the CYP17A1 and NT5C2 genes were associated with decreased visceral and subcutaneous fat area in the Japanese women. Finally, we found that variations in the AGTR1 and PNPLA1 were related to nonalcoholic fatty liver disease(ectopic fat accumulation).

Research Products

• [Journal Article] Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women (2012)
  • Author(s): Hotta K, et al (last)
  • Journal Title: J Hum Genet Volume: 57 Issue: 1 Pages: 46-51
  • DOI: 10.1038/jhg.2011.127
  • Peer Reviewed
• [Journal Article] Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography (2012)
  • Author(s): Hotta K, et al (last)
  • Journal Title: J Hum Genet Volume: (In press) Issue: 5 Pages: 305-310
  • DOI: 10.1038/jhg.2012.21
  • Peer Reviewed
• [Journal Article] Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population (2011)
  • Author(s): Hotta K, et al (last)
  • Journal Title: J Hum Genet Volume: 56 Issue: 9 Pages: 716-719
  • DOI: 10.1038/jhg.2011.74
  • Peer Reviewed
• [Journal Article] Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area (2011)
  • Author(s): Hotta K, et al (last)
  • Journal Title: J Hum Genet Volume: 56 Issue: 10 Pages: 716-719
  • DOI: 10.1038/jhg.2011.86
  • Peer Reviewed
• [Journal Article] Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population (2010)
  • Author(s): Hotta K, Nakamura M, Nakamura T, Matsuo T, Nakata Y, Kamohara S, Miyatake N, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Kawamoto M, Masuzaki H, Ueno T, Hamaguchi K, Tanaka K, Yamada K, Hanafusa
  • Journal Title: J Hum Genet Volume: 55(11) Issue: 11 Pages: 738-742
  • DOI: 10.1038/jhg.2010.99
  • NAID: 10030737572
  • Peer Reviewed
• [Journal Article] Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease (2010)
  • Author(s): Hotta K, Yoneda M, Hyogo H, Ochi H, Mizusawa S, Ueno T, Chayama K, Nakajima A, Nakao K, Sekine A
  • Journal Title: BMC Med Genet Volume: 11(1) Issue: 1 Pages: 172-172
  • DOI: 10.1186/1471-2350-11-172
  • NAID: 120002949731
  • Peer Reviewed
• [Journal Article] Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R I and their effect on visceral fat area in the Japanese population. (2010)
  • Author(s): Hotta K, Nakamura M, Nakamura T, Matsuo T, Nakata Y, Kamohara S, Miyatake N, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Kawamoto M, Masuzaki H, Ueno T, Hamaguchi K, Tanaka K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Nakamura Y, Kamatani N.
  • Journal Title: Journal of Human Genetics Volume: 55 Pages: 738-742
  • Peer Reviewed
• [Journal Article] Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease. (2010)
  • Author(s): Hotta K, Yoneda M, Hyogo H, Ochi H, Mizusawa S, Ueno T, Chayama K, Nakajima A, Nakao K, Sekine A.
  • Journal Title: BMC Medical Genetics Volume: 11 Pages: 172-181
  • NAID: 120002949731
  • Peer Reviewed
• [Journal Article] Screening of 336 single-nucleotide polymorphisms in 85 obesity-related genes revealed McKusick-Kaufman syndrome gene variants are associated with metabolic syndrome (2009)
  • Author(s): Hotta K, Nakamura T, Takasaki J, Takahashi H, Takahashi A, Nakata Y, Kamohara S, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Masuzaki H, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Hamaguchi K, Tanaka K, Yamada K, Hanafusa T, Oikawa S, Yo
  • Journal Title: J Hum Genet Volume: 54(4) Issue: 4 Pages: 230-235
  • DOI: 10.1038/jhg.2009.16
  • NAID: 10030730053
  • Peer Reviewed
• [Journal Article] Association between angiotensin II type 1receptor polymorphisms and the occurrence of nonalcoholic fatty liver disease (2009)
  • Author(s): Yoneda M, Hotta K, Nozaki Y, Endo H, Uchiyama T, Mawatari H, Iida H, Kato S, Fujita K, Takahashi H, Kirikoshi H, Kobayashi N, Inamori M, Abe Y, Kubota K, Saito S, Maeyama S, Wada K Nakajima A
  • Journal Title: Liver Int Volume: 29(7) Issue: 7 Pages: 1078-1085
  • DOI: 10.1111/j.1478-3231.2009.01988.x
  • Peer Reviewed
• [Journal Article] Secretogranin II binds to secretogranin III and forms secretory granules withorexin, neuropeptide Y, and POMC (2009)
  • Author(s): Hotta K, Hosaka M, Tanabe A Takeuchi T
  • Journal Title: J Endocrinol Volume: 202(1) Issue: 1 Pages: 111-121
  • DOI: 10.1677/joe-08-0531
  • Peer Reviewed
• [Journal Article] Influence of inducible nitric oxide synthase polymorphisms in Japanese patients with on-alcoholic fatty liver disease (2009)
  • Author(s): Yoneda M, Hotta K, Nozaki Y, Endo H, Tomeno W, Watanabe S, Hosono K, Mawatari H, Iida H, Fujita K, Takahashi H, Kirikoshi H, Kobayashi N, Inamori M, Kubota K, Shimamura T, Saito S, Maeyama S, Wada K Nakajima A
  • Journal Title: Hepatol Res Volume: 39(10) Issue: 10 Pages: 963-971
  • DOI: 10.1111/j.1872-034x.2009.00539.x
  • Peer Reviewed
• [Journal Article] Association between obesity and polymorphisms inSEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population (2009)
  • Author(s): Hotta K, Nakamura M, Nakamura T, Matsuo T, Nakata Y, Kamohara S, Miyatake N, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Masuzaki H, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Kawamoto M, Ueno T, Hamaguchi K, Tanaka K, Yamada K, Hanafusa
  • Journal Title: J Hum Genet Volume: 54(12) Issue: 12 Pages: 727-731
  • DOI: 10.1038/jhg.2009.106
  • Peer Reviewed
• [Journal Article] Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population (2009)
  • Author(s): Kikuko Hotta
  • Journal Title: Journal of Human Genetics 54 Pages: 727-731
  • NAID: 10030732862
  • Peer Reviewed
• [Presentation] FTO、SH2B1の遺伝子多型は内臓脂肪面積と関連している (2011)
  • Author(s): 堀田紀久子、中田由夫、松尾知明、蒲原聖可、和田淳、小谷一晃、嶺尾郁夫、浜口和之、益崎裕章、船橋徹、宮崎滋、徳永勝人、山田研太郎、田中喜代次、花房俊昭、及川眞一、吉松博信、坂田利家、松澤佑次、中尾一和
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 兵庫県淡路市
  • Year and Date: 2011-09-24
• [Presentation] FTO、SH2B1の遺伝子多型は内臓脂肪面積と関連している (2011)
  • Author(s): 堀田紀久子、中田由夫、松尾知明、蒲原聖可、和田淳、小谷一晃、嶺尾郁夫、浜口和之、益崎裕章、船橋徹、宮崎滋、徳永勝人、山田研太郎、田中喜代次、花房俊昭、及川眞一、吉松博信、坂田利家、松澤佑次、中尾一和
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 兵庫県淡路夢舞台国際会議場
  • Year and Date: 2011-09-24
• [Presentation] PNPLA3遺伝子上のrs738409と非アルコール性脂肪肝炎とのケース・コントロール相関解析 (2011)
  • Author(s): 堀田紀久子、北本卓也、北本綾、米田正人、中島淳、上野隆登、兵庫秀幸、越智秀典、茶山一彰、関根章博、中尾一和
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2011-05-21
• [Presentation] PNPLA3遺伝子上のrs738409と非アルコール性脂肪肝炎とのケース・コントロール相関解析 (2011)
  • Author(s): 堀田紀久子、北本卓也、北本綾、米田正人、中島淳、上野登隆、兵庫秀幸、越智秀典、茶山一彰、関根章博、中尾一和
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 北海道さっぽろ芸術文化の館
  • Year and Date: 2011-05-21
• [Presentation] NRXN3、TFAP2B、MSRA、LYPLAL1、FTO、MC4R遺伝子多型と内臓脂肪面積、皮下脂肪面積との相関 (2011)
  • Author(s): 堀田紀久子、船橋徹、嶺尾郁夫、和田淳、浜口和之、益崎裕章、吉松博信、坂田利家、花房俊昭、松澤佑次、中尾一和
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2011-04-23
• [Presentation] NRXN3、TFAP2B、MSRA、LYPLALI、FTO、MC4R遺伝子多型と内臓脂肪面積、皮下脂肪面積との相関 (2011)
  • Author(s): 堀田紀久子、船橋徹、嶺尾郁夫、和田淳、浜口和之、益崎裕章、吉松博信、坂田利家、花房俊昭、松澤佑次、中尾一和
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 兵庫県神戸国際会議場
  • Year and Date: 2011-04-23
• [Presentation] 欧米人で同定された肥満感受性領域の日本人における検討 (2010)
  • Author(s): 堀田紀久子、中田由夫、松尾知明、蒲原聖可、和田淳、小谷一晃、嶺尾郁夫、浜口和之、益崎裕章、船橋徹、宮崎滋、徳永勝人、田中喜代次、山田研太郎、花房俊昭、及川眞一、吉松博信、坂田利家、松澤佑次、中尾一和
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 群馬県前橋市
  • Year and Date: 2010-10-01
• [Presentation] 欧米人で同定された肥満感受性領域の日本人における検討 (2010)
  • Author(s): 堀田紀久子、中田由夫、松尾知明、蒲原聖可、和田淳、小谷一晃、嶺尾郁夫、浜口和之、益崎裕章、船橋徹、宮崎滋、徳永勝人、田中喜代次、山田研太郎、花房俊昭、及川眞一、吉松博信、坂田利家、松澤佑次、中尾一和
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 群馬県前橋市 前橋テルサ
  • Year and Date: 2010-10-01
• [Presentation] メタボリックシンドローム関連遺伝子の同定 (2010)
  • Author(s): 堀田紀久子、中田由夫、松尾知明、蒲原聖可、和田淳、伊藤直人、嶺尾郁夫、浜口和之、船橋徹、宮崎滋、徳永勝人、益崎裕章、田中喜代次、山田研太郎、花房俊昭、及川眞一、吉松博信、中尾一和、坂田利家、松澤佑次
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山県岡山市
  • Year and Date: 2010-05-29
• [Presentation] メタボリックシンドローム関連遺伝子の同定 (2010)
  • Author(s): 堀田紀久子、中田由夫、松尾知明、蒲原聖可、和田淳、伊藤直人、嶺尾郁夫、浜口和之、船橋徹、宮崎滋、徳永勝人、益崎裕章、田中喜代次、山田研太郎、花房俊昭、及川眞一、吉松博信、中尾一和、坂田利家、松澤佑次
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山県岡山市 岡山コンベンションセンター
  • Year and Date: 2010-05-23
• [Presentation] セクレトグラニン3に結合するセクレトグラニン2の視床下部における意義 (2009)
  • Author(s): 堀田紀久子
  • Organizer: 第30回日本肥満学会
  • Place of Presentation: 静岡県浜松市
  • Year and Date: 2009-10-09
• [Presentation] セクレトグラニン3に結合するセクレトグラニン2の視床下部における意義 (2009)
  • Author(s): 堀田紀久子
  • Organizer: 日本肥満学会
  • Place of Presentation: 静岡県浜松市
  • Year and Date: 2009-10-09
• [Presentation] Screening of 336 single nucleotide polymorphisms(SNPs) in 85obesity-related genes revealed that MKKS and MYO9A variants are associated with metabolic syndrome (2009)
  • Author(s): Hotta K, Nakamaura T. Wada J, Masuzaki H, Funahashi T, Hamaguchi K, Tanaka K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K Kamatani N
  • Organizer: 45th General Assembly of the European Association for the Study of Diabetes
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2009-10-01
• [Presentation] 欧米人ゲノムワイド関連解析で同定された肥満感受性領域と日本人における高度肥満との関連 (2009)
  • Author(s): 堀田紀久子
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 東京都品川区
  • Year and Date: 2009-09-24
• [Presentation] 欧米人ゲノムワイド関連解析で同定された肥満感受性領域と日本人における高度肥満との関連 (2009)
  • Author(s): 堀田紀久子、中村道大、草野律子、浜口和之、中村佑輔
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京都品川区
  • Year and Date: 2009-05-24
• [Presentation] 非アルコール性脂肪肝障害(NAFLD)とAGTR1多型との相関解析 (2009)
  • Author(s): 堀田紀久子、米田正人、中島淳
  • Organizer: 第52回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2009-05-24
• [Presentation] 肥満発症における視床下部の役割-遺伝子多型解析からのアプローチ (2009)
  • Author(s): 堀田紀久子、穂坂正博、竹内利行
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬県前橋市
  • Year and Date: 2009-04-23