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2012 Fiscal Year Final Research Report

Recurrent pregnancy loss -associated promoter polymorphisms affect ANXA5 ge ne expression via G -quadruplex propensity

Research Project

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Project/Area Number 23659182
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Human genetics
Research InstitutionFujita Health University

Principal Investigator

KURAHASHI Hiroki  藤田保健衛生大学, 総合医科学研究所, 教授 (30243215)

Project Period (FY) 2011 – 2012
Keywords習慣流産 / アネキシン A5 / グアニン 4 重鎖 / プロモーター / 多型 / 円旋光二色性
Research Abstract

Recent findings have highlighted the possibility that polymorphismswithin the annexin A5 gene (ANXA5) promoter contribute to the etiology of various obstetriccomplications. However, the underlying mechanisms are unknown. In our present study, thetranscriptional activity of the ANXA5gene promoter was examined in the context of G-quadruplexformation. The M2 haplotype of the promoter polymorphisms that confers a high risk of onset forthese disorders shows lower activity and less expression of ANXA5 mRNA. This gene promoterregion has a motif that potentially forms a G-quadruplex structure, and the M2 allele possesses lesspotential than the major allele. The promoter activity determined by luciferase reporter analysiscorrelated with the in vitro G-quadruplex propensity estimated by circular dichroism. Treatmentwith a G-quadruplex ligand inhibited this promoter activity. Taken together, our data indicate thatthe M2 allele instigates G-quadruplex-mediated transcriptional regulation and consequentlydownregulates the placental anticoagulation factor annexin A5 levels, leading to obstetric disorders.Our data lend support to the developing paradigm that genomic variation affects gene expressionlevels via DNA secondary structures leading to the disease susceptibility.

  • Research Products

    (41 results)

All 2013 2012 2011 Other

All Journal Article (24 results) (of which Peer Reviewed: 24 results) Presentation (14 results) Remarks (3 results)

  • [Journal Article] Two sequential cleavage reactions on cruciform DNA structures cause palindrome -mediated chromosomal translocations2013

    • Author(s)
      Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, Emanuel BS, Kurahashi H
    • Journal Title

      Nat Commun

      Volume: 4 Pages: 1592

    • DOI

      doi:10.1038/ncomms2595

    • Peer Reviewed
  • [Journal Article] MTA3 regulates CGB5 and Snail genes in trophoblast2013

    • Author(s)
      Chen Y, Miyazaki J, Nishizawa H, Kurahashi H, Leach R, Wang K.
    • Journal Title

      Biochem Biophys Res Commun

    • DOI

      doi:pii:S0006-291X(13)00412-9. 10.1016/j.bbrc.2013. 02.102.

    • Peer Reviewed
  • [Journal Article] Chromosomal translocations and palindromic AT-rich repeats2012

    • Author(s)
      Kato T, Kurahashi H, Emanuel BS
    • Journal Title

      Curr Opin Genet Dev

      Volume: 22 Pages: 221-228

    • DOI

      doi:10.1016/j.gde2012.02.004.

    • Peer Reviewed
  • [Journal Article] HORMAD1-dependent checkpoint/surveillance mechanism eliminates asynaptic oocytes2012

    • Author(s)
      Kogo H, Tsutsumi M, Ohye T, Inagaki H, Abe T, Kurahashi H
    • Journal Title

      Genes Cells

      Volume: 17 Pages: 439-454

    • DOI

      doi:10.1111/j.1365-2443.2012.01600.x

    • Peer Reviewed
  • [Journal Article] HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity2012

    • Author(s)
      Kogo H, Tsutsumi M, Ohye T, Inagaki H, Kiyonari H, Kurahashi H
    • Journal Title

      Genes Cells

      Volume: 17 Pages: 897-912

    • DOI

      doi:10.1111/gtc.12005.

    • Peer Reviewed
  • [Journal Article] Failure of homologous synapsis and sex-specific reproduction problems2012

    • Author(s)
      Kurahashi H, Kogo H, Tsutsumi M, Inagaki H, Ohye T
    • Journal Title

      Front Genet

      Volume: 3 Pages: 112

    • DOI

      doi:10.3389/ fgene.2012.00112

    • Peer Reviewed
  • [Journal Article] Molecular basis of maternal age-related increase in oocyte aneuploidy2012

    • Author(s)
      Kurahashi H, Tsutsumi M, Nishiyama S, Kogo H, Inagaki H, Ohye T
    • Journal Title

      Congenit Anom (Kyoto)

      Volume: 52 Pages: 8-15

    • DOI

      doi:10.1111/j.1741-4520.2011.00350.x

    • Peer Reviewed
  • [Journal Article] Mechanism of complex gross chromosomal rearrangements: A commentary on Concomitant microduplications of MECP2 and ATRX in male patients with severe mental retardation.2012

    • Author(s)
      Kurahashi H, Ohye T, Inagaki H, Kogo H, Tsutsumi M
    • Journal Title

      J Hum Genet

      Volume: 57 Pages: 81-3

    • DOI

      doi:10.1038/jhg.2011.143.

    • Peer Reviewed
  • [Journal Article] Screening of genes involved in chromosome segregation during meiosis I: in vitro gene transfer to mouse fetal oocytes.2012

    • Author(s)
      Tsutsumi M, Kowa-Sugiyama H, Bolor H, Kogo H, Inagaki H, Ohye T, Yamada K, Taniguchi-Ikeda M, Toda T, Kurahashi H.
    • Journal Title

      J Hum Genet

      Volume: 57 Pages: 515-22

    • DOI

      doi:10.1038/jhg.2012.61.

    • Peer Reviewed
  • [Journal Article] Kurahashi H, Udagawa Y. Upregulation of HtrA4 in the placentas of patients with severe pre-eclampsia2012

    • Author(s)
      Inagaki A, Nishizawa H, Ota S, Suzuki M, Inuzuka H, Miyamura H, Sekiya T
    • Journal Title

      Placenta

      Volume: 33 Pages: 919-26

    • DOI

      doi:10.1016/j.placenta.2012.08.003

    • Peer Reviewed
  • [Journal Article] Serum neutrophil gelatinase-associated lipocalin during the early postoperative period predicts the recovery of graft function after kidney transplantation from donors after cardiac death2012

    • Author(s)
      Kusaka M, Iwamatsu F, Kuroyanagi Y, Nakaya M, Ichino M, Marubashi S, Nagano H, Shiroki R, Kurahashi H, Hoshinaga K
    • Journal Title

      J Urol

      Volume: 187 Pages: 2261-2267

    • DOI

      doi:10.1016/j.juro.2012.01.033.

    • Peer Reviewed
  • [Journal Article] A Functional variation in the hypocretin neuropeptide precursor gene may be associated with obstructive sleep apnea syndrome in Japan2012

    • Author(s)
      Ahmed WA, Tsutsumi M, Nakata S, Mori T, Nishimura Y, Fujisawa T, Kato I, Nakashima M, Kurahashi H, Suzuki K.
    • Journal Title

      Laryngoscope

      Volume: 122 Pages: 925-929

    • DOI

      doi:10.1002/lary.23179.

    • Peer Reviewed
  • [Journal Article] Global gene expression profiling in PPAR-γ agonist-treated kidneys in an orthologous rat model of human autosomal recessive polycystic kidney disease2012

    • Author(s)
      Yoshihara D, Kugita M, Yamaguchi T, Aukema HM, Kurahashi H, Morita M, Hiki Y,Calvet JP, Wallace DP, Toyohara T, Abe T,Nagao S.
    • Journal Title

      PPAR Research

      Pages: 695898

    • DOI

      doi:10.1155/2012/695898

    • Peer Reviewed
  • [Journal Article] DNA secondary structure is influenced by genetic variation and alters susceptibility to de novo translocation2011

    • Author(s)
      Kato T, Inagaki H, Tong M, Kogo H, Ohye T, Yamada K, Tsutsumi M, Emanuel BS,Kurahashi H.
    • Journal Title

      Mol Cytoenet

      Volume: 4 Pages: 18

    • DOI

      doi:10.1186/1755-8166-4-18

    • Peer Reviewed
  • [Journal Article] Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy2011

    • Author(s)
      Taniguchi-Ikeda M, Kobayashi K, Kanagawa M, Yu CC, Mori K, Oda T, Kuga A, Kurahashi H, Akman HO, DiMauro S, Kaji R, Yokota T, Takeda S, Toda T
    • Journal Title

      Nature

      Volume: 478 Pages: 127-131

    • DOI

      doi:10.1038/nature10456

    • Peer Reviewed
  • [Journal Article] Characterization of a novel mouse gene encoding an SYCP3-like protein that re-localizes from the XY body to the nucleolus during prophase of male meiosis I2011

    • Author(s)
      Tsutsumi M, Kogo H, Kowa-Sugiyama H, Inagaki H, Ohye T, Kurahashi H.
    • Journal Title

      Biol Reprod

      Volume: 85 Pages: 165-171

    • DOI

      doi:10.1095/biolreprod.110.087270

    • Peer Reviewed
  • [Journal Article] Polymorphism in annexin A5 gene promoter in Japanese women with recurrent pregnancy loss2011

    • Author(s)
      Miyamura H, Nishizawa H, Ota S, Suzuki M, Inagaki A, Egusa H, Nishiyama S, Kato T, Pryor-Koishi K, Nakanishi I, Fujita T, Imayoshi Y, Markoff A, Yanagihara I, Udagawa Y, Kurahashi H
    • Journal Title

      Mol Hum Reprod

      Volume: 17 Pages: 447-452

    • DOI

      doi:10.1093/molehr/gar008.

    • Peer Reviewed
  • [Journal Article] A rare synaptonemal complex protein 3 gene varian in unexplained female infertility2011

    • Author(s)
      Nishiyama S, Kishi T, Kato T, Suzuki M, Bolor H, Udagawa Y, Kurahashi H.
    • Journal Title

      Mol Hum Reprod

      Volume: 17 Pages: 266-271

    • DOI

      doi:10.1093/molehr/gaq098.

    • Peer Reviewed
  • [Journal Article] Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction.2011

    • Author(s)
      Nishizawa H, Ota S, Suzuki M, Kato T, Sekiya T, Kurahashi H, Udagawa Y
    • Journal Title

      Reprod Biol Endocrinol

      Volume: 9 Pages: 107

    • DOI

      doi:10.1186/1477-7827-9-107

    • Peer Reviewed
  • [Journal Article] Impact of indoleamine 2,3-dioxygenase on the antioxidant system in the placentas of severely pre-eclamptic patients2011

    • Author(s)
      Nishizawa H, Suzuki M, Pryor-Koishi K,Sekiya T, Tada S, Kurahashi H, Udagawa Y
    • Journal Title

      Syst Biol Reprod Med

      Volume: 57 Pages: 174-178

    • DOI

      doi:10.3109/19396368.2011.587590.

    • Peer Reviewed
  • [Journal Article] Global gene expression profiling in early-stage polycystic kidney disease in the Han : SPRD Cy rat identifies a role for RXR signaling2011

    • Author(s)
      Kugita M, Nishii K, Morita M, Yoshihara D, Kowa-Sugiyama H, Yamada K, Yamaguchi T, Wallace DP, Calvet JP, Kurahashi H, Nagao S.
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: 300 Pages: F177-88

    • DOI

      doi:10.1152/ajprenal.00470.2010.

    • Peer Reviewed
  • [Journal Article] PPAR-{gamma} agonist ameliorates kidney and liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease.2011

    • Author(s)
      Yoshihara D, Kurahashi H, Morita M, Kugita M, Hiki Y, Aukema HM, Yamaguchi T,Calvet JP, Wallace DP, Nagao S
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: 300 Pages: F465-74

    • DOI

      doi:10.1152/ajprenal.00460.2010.

    • Peer Reviewed
  • [Journal Article] Lack of Association between Orexin Receptor Genes Polymorphisms and Obstructive Sleep Apnea Syndrome in Japanese2011

    • Author(s)
      Ahmed WA, Mori T, Nishimura Y, Kitanaka T, Kato T, Bhardwaj KA, Kurahashi H, Suzuki K.
    • Journal Title

      Sleep Biol Rhythms

      Volume: 9 Pages: 73-77

    • Peer Reviewed
  • [Journal Article] Acute eosinophilic pneumonia occurring in a dedicator of cytokinesis 8 (DOCK8) deficient patient.

    • Author(s)
      Tsuge I, Ito K, Ohye T, Kando N, Kondo Y, Nakajima Y, Inuo C, Kurahashi H, Urisu A.
    • Journal Title

      Pediatric Pulmonology

      Volume: (in press)

    • Peer Reviewed
  • [Presentation] Pathogenic exon-trapping by SVA retrotransposon and rescue in Faukuyama muscular dystrophy2012

    • Author(s)
      Taniguchi M, Kobayashi K, Kanagawa M, Yu CC, Oda T, Kuga A, Kurahashi H, Akmen HO,DiMauro S, Yokota T, Takeda S, Toda T
    • Organizer
      ASHG 2012, annual meeting
    • Place of Presentation
      San Francisco
    • Year and Date
      20121106-10
  • [Presentation] Obstetric complication-associated ANXA5promoter polymorphisms affect gene expression via DNA secondary structures2012

    • Author(s)
      Inagaki H, Ota S, Nishizawa H, Miyamura H, Nakahira K, Suzuki M, Nishiyama S, Udagawa Y, Yanagihara I, Kurahashi H.
    • Organizer
      ASHG 2012, annual meeting
    • Place of Presentation
      San Francisco
    • Year and Date
      20121106-10
  • [Presentation] Polymorphisms in the ANXA5gene promoter in Japanese women with preeclampsia2012

    • Author(s)
      Miyamura H, Nishizawa H, Ota S,Suzuki M, Inagaki A, Egusa H, Nishiyama S, Kurahashi H, Udagawa Y.
    • Organizer
      The XX FIGO World Congress
    • Place of Presentation
      Rome, Italy
    • Year and Date
      20121007-12
  • [Presentation] Mechanism of recurrent translocation t(11;22) initiated by cruciform conformation of palindromes2012

    • Author(s)
      Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kurahashi H.
    • Organizer
      FASEB SRC:"Dynamic DNA structures in biology
    • Place of Presentation
      Saxtons River, USA
    • Year and Date
      20120617-22
  • [Presentation] Mechanism of recurrent translocation t(11;22) initiated by cruciform conformation of palindromic sequences2011

    • Author(s)
      Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, Emanuel BS, Kurahashi H.
    • Organizer
      The 12th International Congress of Human Genetics
    • Place of Presentation
      Montreal,Canada
    • Year and Date
      20111011-15
  • [Presentation] Identification of a novel palindrome mediated translocation associated with the t(3;8) of hereditary renal cancer2011

    • Author(s)
      Kato T, Sheridan MB, Hacker AM, Inagaki H, Glover TW, Plon SE, Drabkin HA, Gemmill RM, Kurahashi H, Emanuel BS
    • Organizer
      The 12th International Congress of Human Genetics
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      20111011-15
  • [Presentation] Identification of a recombination hotspot sequence at the breakpoint region of the 22q11 deletion using a yeast model2011

    • Author(s)
      Ohye T, Inagaki H, Kogo H, Tsutsumi M, Emanuel BS, Kurahashi H.
    • Organizer
      The 12th International Congress of Human Genetics
    • Place of Presentation
      Montreal,Canada
    • Year and Date
      20111011-15
  • [Presentation] HORMAD1-deficiency causes azoospermia in males and pregnancy loss in females2011

    • Author(s)
      Kogo H, Tsutsumi M, Ohye T, Inagaki H,Kurahashi H.
    • Organizer
      The 12th International Congress of Human Genetics
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      20111011-15
  • [Presentation] Mutation in the SYCP3 gene identified in a woman with recurrent pregnancy loss affect the synaptonemal complex conformation at meiotic prophase I2011

    • Author(s)
      Tsutsumi M, Kogo H, Inagaki H, Ohye T,Kurahashi H.
    • Organizer
      The 12th International Congress of Human Genetics, Montreal
    • Place of Presentation
      Canada
    • Year and Date
      20111011-15
  • [Presentation] Polymorphisms in the ANXA5gene promoter in Japanese women with pre-eclampsia2011

    • Author(s)
      Kurahashi H, Miyamura H, Nishizawa H, Ota S,Suzuki M, Inagaki A, Egusa H, Nishiyama S, Udagawa Y.
    • Organizer
      European Society of Human Genetics Conference 2012.
    • Place of Presentation
      Nurnberg,Germany
    • Year and Date
      20110623-26
  • [Presentation] Polymorphisms in the annexin A5 gene promoter in Japanese women with recurrent pregnancy loss2011

    • Author(s)
      Miyamura H, Nishizawa H, Ota S, Suzuki M, Inagaki A, Egusa H, Nishiyama S, Kato T, Pryor-Koishi K, Nakanishi I, Fujita T,Imayoshi Y, Markoff A, Yanagihara I,Udagawa Y, Kurahashi H.
    • Organizer
      27th Annual Meeting of ESHRE - Stockholm 2011
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      20110603-06
  • [Presentation] Polymorphisms in the annexin A5 gene promoter in Japanese women with recurrent pregnancy loss2011

    • Author(s)
      Kurahashi H, Miyamura H, Nishizawa H, Ota S, Suzuki M, Inagaki A, Egusa H, Nishiyama S, Kato T, Pryor-Koishi K, Nakanishi I, Fujita T, Imayoshi Y, Negi R, Markoff A, Yanagihara I, Udagawa, Y.
    • Organizer
      European Society of Human Genetics Conference 2011.
    • Place of Presentation
      Amsterdam, Netherlands
    • Year and Date
      20110528-31
  • [Presentation] Polymorphisms in the annexin A5 gene promoter in Japanese women with recurrent pregnancy loss2011

    • Author(s)
      Miyamura H, Nishizawa H, Ota S, Suzuki M, Inagaki A, Egusa H, Nishiyama S, Kato T, Pryor-Koishi K, Nakanishi I, Fujita T, Imayoshi Y, Markoff A, Yanagihara I, Udagawa Y, Kurahashi H.
    • Organizer
      59th Annual Clinical Meeting, ACOG
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      20110430-0504
  • [Presentation] GEN1 resolves cruciform-forming palindromic DNA leading to a recurrent translocation in humans. Keystone Symposia: Functional Consequences of Structural Variation in the Genome2011

    • Author(s)
      Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, Emanuel BS, Kurahashi H.
    • Organizer
      Steamboat Springs
    • Place of Presentation
      Colorado, USA
    • Year and Date
      20110108-13
  • [Remarks] 藤田保健衛生大学・総合医科学研究所

    • URL

      http://www.fujita-hu.ac.jp/ICMS/

  • [Remarks] 分子遺伝学研究部門

    • URL

      http://www.fujita-hu.ac.jp/?genome/mg/

  • [Remarks] 研究代表者が運営

    • URL

      http://www.fujita-hu.ac.jp/?genome/11&22/

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Published: 2014-09-25  

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