Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
June-2016 Volume 13 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2016 Volume 13 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Hedgehog gene polymorphisms are associated with the risk of Hirschsprung's disease and anorectal malformation in a Chinese population

  • Authors:
    • Hong Gao
    • Dajia Wang
    • Yuzuo Bai
    • Juan Zhang
    • Mei Wu
    • Jie Mi
    • Huimin Jia
    • Weilin Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Pediatric Surgery, Jinzhou Women and Children's Hospital, Jinzhou, Liaoning 121000, P.R. China, Department of General Surgery, Children's Hospital of Hebei, Shijiazhuang, Hebei 050031, P.R. China
  • Pages: 4759-4766
    |
    Published online on: April 15, 2016
       https://doi.org/10.3892/mmr.2016.5139
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Hedgehog (HH) is one of the key morphogens expressed in the gut mesenchyme that control animal development and tissue homeostasis. The HH gene has been shown to be closely associated with Hirschsprung's disease (HSCR) and anorectal malformations (ARMs); thus, it was hypothesized that HH signaling pathway‑associated genes may be candidate genes for HSCR and ARMs. The present study aimed to evaluate whether polymorphisms in the HH gene were associated with HSCR and ARM in a Chinese population. HH gene variants (rs61730970, rs200798148 and rs146535482) were analyzed in whole blood samples from patients with HSCR and ARMs, as well as normal children (control group). The results suggested that, when the rs61730970, rs200798148 and rs146535482 alleles of the HH gene lacked particular single nucleotide polymorphisms (SNPs), the patients were associated with a greater risk of HSCR and/or ARM [HSCR: odds ratio (OR)=1.543, P=0.004; OR=1.494, P=0.007; rs146535482: OR=1.556, P=0.003, respectively. ARM: OR=1.528, P=0.045; OR=1.800, P=0.007; OR=1.743, P=0.009, respectively). Sequencing of rs61730970 and rs200798148 revealed a loss of heterozygosity and SNPs at these loci in patients with HSCR. Similarly, the sequencing of rs61730970 and rs146535482 revealed a loss of heterozygosity and SNPs at these loci in patients with ARM. Although preliminary, these results suggested that the HH gene may be involved in genetic interactions associated with the pathogenesis of HSCR and ARM.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Amiel J, Sproat-Emison E, Garcia-Barcelo M, Lantieri F, Burzynski G, Borrego S, Pelet A, Arnold S, Miao X, Griseri P, et al: Hirschsprung disease, associated syndromes and genetics: A review. J Med Genet. 45:1–14. 2008. View Article : Google Scholar

2 

Saeed A, Barreto L, Neogii SG, Loos A, McFarlane I and Aslam A: Identification of novel genes in Hirschsprung disease pathway using whole genome expression study. J Pediatr Surg. 47:303–307. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Passarge E and Bruder E: Genetic bases of Hirschsprung's disease. Pathologe. 28:113–118. 2007.In German. View Article : Google Scholar : PubMed/NCBI

4 

El-Nachef W and Grikscheit T: Enteric nervous system cell replacement therapy for Hirschsprung disease: Beyond tissue-engineered intestine. Eur J Pediatr Surg. 24:214–218. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Rintala RJ: Congenital anorectal malformations: Anything new? J Pediatr Gastroenterol Nutr. 48(Suppl 2): S79–S82. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Bán G, Németh P and Túri S: Neurovesical dysfunction in children with anorectal malformations. Orv Hetil. 147:1645–1649. 2006.In Hungarian.

7 

Sánchez-Mejías A, Fernández RM, López-Alonso M, Antiñolo G and Borrego S: New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease. Genet Med. 12:39–43. 2010. View Article : Google Scholar

8 

Pan ZW, Lou J, Luo C, Yu L and Li JC: Association analysis of the SOX10 polymorphism with Hirschsprung disease in the Han Chinese population. J Pediatr Surg. 46:1930–1934. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Fernandez RM, Ruiz-Ferrer M, Lopez-Alonso M, Antiñolo G and Borrego S: Polymorphisms in the genes encoding the 4 RET ligands, GDNF, NTN, ARTN, PSPN, and susceptibility to Hirschsprung disease. J Pediatr Surg. 43:2042–2047. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Kwon MJ, Lee GH, Lee MK, Kim JY, Yoo HS, Ki CS, Chang YS, Kim JW and Park WS: PHOX2B mutations in patients with Ondine-Hirschsprung disease and a review of the literature. Eur J Pediatr. 170:1267–1271. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Gregory-Evans CY, Vieira H, Dalton R, Adams GG, Salt A and Gregory-Evans K: Ocular coloboma and high myopia with Hirschsprung disease associated with a novel ZFHX1B missense mutation and trisomy 21. Am J Med Genet A. 131:86–90. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Seifert AW, Harfe BD and Cohn MJ: Cell lineage analysis demonstrates an endodermal origin of the distal urethra and perineum. Dev Biol. 318:143–152. 2008. View Article : Google Scholar : PubMed/NCBI

13 

van den Brink GR: Hedgehog signaling in development and homeostasis of the gastrointestinal tract. Physiol Rev. 87:1343–1375. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Torihashi S, Hattori T, Hasegawa H, Kurahashi M, Ogaeri T and Fujimoto T: The expression and crucial roles of BMP signaling in development of smooth muscle progenitor cells in the mouse embryonic gut. Differentiation. 77:277–289. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Zacchetti G, Duboule D and Zakany J: Hox gene function in vertebrate gut morphogenesis: The case of the cecum. Development. 134:3967–3973. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Fairbanks TJ, De Langhe S, Sala FG, Warburton D, Anderson KD, Bellusci S and Burns RC: Fibroblast growth factor 10 (Fgf10) invalidation results in anorectal malformation in mice. J Pediatr Surg. 39:360–365; discussion 360–365. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Tai CC, Sala FG, Ford HR, Wang KS, Li C, Minoo P, Grikscheit TC and Bellusci S: Wnt5a knock-out mouse as a new model of anorectal malformation. J Surg Res. 156:278–282. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Ngan ES, Garcia-Barceló MM, Yip BH, Poon HC, Lau ST, Kwok CK, Sat E, Sham MH, Wong KK, Wainwright BJ, et al: Hedgehog/Notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans. J Clin Invest. 121:3467–3478. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Lees C, Howie S, Sartor RB and Satsangi J: The hedgehog signalling pathway in the gastrointestinal tract: Implications for development, homeostasis, and disease. Gastroenterology. 129:1696–1710. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Odent S, Atti-Bitach T, Blayau M, Mathieu M, Aug J, Delezo de AL, Gall JY, Le Marec B, Munnich A, David V and Vekemans M: Expression of the Sonic hedgehog (SHH) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly. Hum Mol Genet. 8:1683–1689. 1999. View Article : Google Scholar : PubMed/NCBI

21 

Chan LH, Wang W, Yeung W, Deng Y, Yuan P and Mak KK: Hedgehog signaling induces osteosarcoma development through Yap1 and H19 overexpression. Oncogene. 33:4857–4866. 2014. View Article : Google Scholar

22 

Casey JP, Magalhaes T, Conroy JM, Regan R, Shah N, Anney R, Shields DC, Abrahams BS, Almeida J, Bacchelli E, et al: A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. Hum Genet. 131:565–579. 2012. View Article : Google Scholar :

23 

Lu J, Yang L, Zhao H, Liu B, Li Y, Wu H, Li Q, Zeng B, Wang Y, Ji W and Zhou Y: The polymorphism and haplotypes of PIN1 gene are associated with the risk of lung cancer in Southern and Eastern Chinese populations. Hum Mutat. 32:1299–1308. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Yang L, Li Y, Cheng M, Huang D, Zheng J, Liu B, Ling X, Li Q, Zhang X, Ji W, et al: A functional polymorphismatmi- croRNA-629-binding site in the 3′-untranslated region of NBS1 gene confers an increased risk of lung cancer in Southern and Eastern Chinese population. Carcinogenesis. 33:338–347. 2012. View Article : Google Scholar

25 

Moore SW: Associations of anorectal malformations and related syndromes. Pediatr Surg Int. 29:665–676. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Ingham PW, Nakano Y and Seger C: Mechanisms and functions of Hedgehog signalling across the metazoa. Nat Rev Genet. 12:393–406. 2011. View Article : Google Scholar : PubMed/NCBI

27 

McMahon AP, Ingham PW and Tabin CJ: Developmental roles and clinical significance of hedgehog signaling. Curr Top Dev Biol. 53:1–114. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Porter JA, Ekker SC, Park WJ, von Kessler DP, Young KE, Chen CH, Ma Y, Woods AS, Cotter RJ, Koonin EV and Beachy PA: Hedgehog patterning activity: Role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain. Cell. 86:21–34. 1996. View Article : Google Scholar : PubMed/NCBI

29 

Porter JA, Young KE and Beachy PA: Cholesterol modification of hedgehog signaling proteins in animal development. Science. 274:255–259. 1996. View Article : Google Scholar : PubMed/NCBI

30 

Pepinsky RB, Zeng C, Wen D, Rayhorn P, Baker DP, Williams KP, Bixler SA, Ambrose CM, Garber EA, Miatkowski K, et al: Identification of a palmitic acid-modified form of human Sonic hedgehog. J Biol Chem. 273:14037–14045. 1998. View Article : Google Scholar : PubMed/NCBI

31 

Mann RK and Beachy PA: Novel lipid modifications of secreted protein signals. Annu Rev Biochem. 73:891–923. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Pettigrew CA, Asp E and Emerson CP Jr: A new role for Hedgehogs in juxtacrine signaling. Mech Dev. 131:137–149. 2014. View Article : Google Scholar :

33 

Jiang SQ and Paulus H: A high-throughput, homogeneous, fluorescence polarization assay for inhibitors of hedgehog protein autoprocessing. J Biomol Screen. 15:1082–1087. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Tokhunts R, Singh S, Chu T, D'Angelo G, Baubet V, Goetz JA, Huang Z, Yuan Z, Ascano M, Zavros Y, et al: The full-length unprocessed hedgehog protein is an active signaling molecule. J Biol Chem. 285:2562–2568. 2010. View Article : Google Scholar :

35 

Palm W, Swierczynska MM, Kumari V, Ehrhart-Bornstein M, Bornstein SR and Eaton S: Secretion and signaling activities of lipoprotein-associated hedgehog and non-sterol-modified hedgehog in flies and mammals. PLoS Biol. 11:e10015052013. View Article : Google Scholar : PubMed/NCBI

36 

Lee JD, Kraus P, Gaiano N, Nery S, Kohtz J, Fishell G, Loomis CA and Treisman JE: An acylatable residue of Hedgehog is differentially required in Drosophila and mouse limb development. Dev Biol. 233:122–136. 2001. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Gao H, Wang D, Bai Y, Zhang J, Wu M, Mi J, Jia H and Wang W: Hedgehog gene polymorphisms are associated with the risk of Hirschsprung's disease and anorectal malformation in a Chinese population. Mol Med Rep 13: 4759-4766, 2016.
APA
Gao, H., Wang, D., Bai, Y., Zhang, J., Wu, M., Mi, J. ... Wang, W. (2016). Hedgehog gene polymorphisms are associated with the risk of Hirschsprung's disease and anorectal malformation in a Chinese population. Molecular Medicine Reports, 13, 4759-4766. https://doi.org/10.3892/mmr.2016.5139
MLA
Gao, H., Wang, D., Bai, Y., Zhang, J., Wu, M., Mi, J., Jia, H., Wang, W."Hedgehog gene polymorphisms are associated with the risk of Hirschsprung's disease and anorectal malformation in a Chinese population". Molecular Medicine Reports 13.6 (2016): 4759-4766.
Chicago
Gao, H., Wang, D., Bai, Y., Zhang, J., Wu, M., Mi, J., Jia, H., Wang, W."Hedgehog gene polymorphisms are associated with the risk of Hirschsprung's disease and anorectal malformation in a Chinese population". Molecular Medicine Reports 13, no. 6 (2016): 4759-4766. https://doi.org/10.3892/mmr.2016.5139
Copy and paste a formatted citation
x
Spandidos Publications style
Gao H, Wang D, Bai Y, Zhang J, Wu M, Mi J, Jia H and Wang W: Hedgehog gene polymorphisms are associated with the risk of Hirschsprung's disease and anorectal malformation in a Chinese population. Mol Med Rep 13: 4759-4766, 2016.
APA
Gao, H., Wang, D., Bai, Y., Zhang, J., Wu, M., Mi, J. ... Wang, W. (2016). Hedgehog gene polymorphisms are associated with the risk of Hirschsprung's disease and anorectal malformation in a Chinese population. Molecular Medicine Reports, 13, 4759-4766. https://doi.org/10.3892/mmr.2016.5139
MLA
Gao, H., Wang, D., Bai, Y., Zhang, J., Wu, M., Mi, J., Jia, H., Wang, W."Hedgehog gene polymorphisms are associated with the risk of Hirschsprung's disease and anorectal malformation in a Chinese population". Molecular Medicine Reports 13.6 (2016): 4759-4766.
Chicago
Gao, H., Wang, D., Bai, Y., Zhang, J., Wu, M., Mi, J., Jia, H., Wang, W."Hedgehog gene polymorphisms are associated with the risk of Hirschsprung's disease and anorectal malformation in a Chinese population". Molecular Medicine Reports 13, no. 6 (2016): 4759-4766. https://doi.org/10.3892/mmr.2016.5139
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team