2012 Fiscal Year Final Research Report
Recurrent pregnancy loss -associated promoter polymorphisms affect ANXA5 ge ne expression via G -quadruplex propensity
Project/Area Number |
23659182
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Human genetics
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Research Institution | Fujita 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)
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Project Period (FY) |
2011 – 2012
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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.
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[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.
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Journal Title
PPAR Research
Pages: 695898
DOI
Peer Reviewed
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[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
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Journal Title
Nature
Volume: 478
Pages: 127-131
DOI
Peer Reviewed
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[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
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Journal Title
Mol Hum Reprod
Volume: 17
Pages: 447-452
DOI
Peer Reviewed
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[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.
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Journal Title
Am J Physiol Renal Physiol
Volume: 300
Pages: F177-88
DOI
Peer Reviewed
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[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
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[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
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[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
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[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
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[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
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[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
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