Obstetric complication-associated ANXA5 promoter polymorphisms may affect gene expression via DNA secondary structures

Hidehito Inagaki, Sayuri Ota, Haruki Nishizawa, Hironori Miyamura, Kumiko Nakahira, Machiko Suzuki, Sachie Nishiyama, Takema Kato, Itaru Yanagihara, Hiroki Kurahashi

Research output: Contribution to journalArticle

Abstract

Recent findings have highlighted the possibility that polymorphisms within the annexin A5 gene (ANXA5) promoter contribute to the etiology of various obstetric complications. However, the underlying mechanisms are unknown. The M2 haplotype of the ANXA5 shows lower activity and less expression of ANXA5 mRNA. This gene promoter region has a motif that potentially forms a G-quadruplex structure. In vitro G-quadruplex propensity estimated by circular dichroism indicated that the M2 haplotype oligonucleotide manifested a decreased potential for G-quadruplex formation. In addition, in vivo G-quadruplex formation of the promoter region was evidenced by the presence of single-stranded DNA shown by sodium bisulfite treatment of placental genomic DNA. Comparative analysis indicated less potential in the M2 allele than the major allele. Promoter activity of the two haplotypes determined by luciferase reporter analysis correlated with the estimated G-quadruplex propensity. Our data lend support to the developing paradigm that genomic variation affects gene expression levels via DNA secondary structures leading to the disease susceptibility.

Original languageEnglish
Pages (from-to)459-466
Number of pages8
JournalJournal of Human Genetics
Volume64
Issue number5
DOIs
Publication statusPublished - 01-05-2019

Fingerprint

G-Quadruplexes
Annexin A5
Obstetrics
Gene Expression
DNA
Haplotypes
Genes
Genetic Promoter Regions
Alleles
Single-Stranded DNA
Disease Susceptibility
Circular Dichroism
Luciferases
Oligonucleotides
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Inagaki, Hidehito ; Ota, Sayuri ; Nishizawa, Haruki ; Miyamura, Hironori ; Nakahira, Kumiko ; Suzuki, Machiko ; Nishiyama, Sachie ; Kato, Takema ; Yanagihara, Itaru ; Kurahashi, Hiroki. / Obstetric complication-associated ANXA5 promoter polymorphisms may affect gene expression via DNA secondary structures. In: Journal of Human Genetics. 2019 ; Vol. 64, No. 5. pp. 459-466.
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Obstetric complication-associated ANXA5 promoter polymorphisms may affect gene expression via DNA secondary structures. / Inagaki, Hidehito; Ota, Sayuri; Nishizawa, Haruki; Miyamura, Hironori; Nakahira, Kumiko; Suzuki, Machiko; Nishiyama, Sachie; Kato, Takema; Yanagihara, Itaru; Kurahashi, Hiroki.

In: Journal of Human Genetics, Vol. 64, No. 5, 01.05.2019, p. 459-466.

Research output: Contribution to journalArticle

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AU - Suzuki, Machiko

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AU - Yanagihara, Itaru

AU - Kurahashi, Hiroki

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