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Vol. 63 No. 2: Issue 2

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TGFíŸ3 / SfaN1 gene variant and the risk factor of nonsyndromic cleft palate only among Indonesian patients

https://doi.org/10.14715/cmb/2017.63.2.13
S. L. Nasroen
Oral and Maxillofacial Surgery Department, Dentistry Study Program Faculty of Medicine, Universitas Jenderal Achmad Yani Cimahi – Bandung Indonesia
A. Tajrin
Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Universitas Hasanuddin Makassar Indonesia
P. N. Fauziah
Department of Medical Laboratory Technology, School of Health Sciences Jenderal Achmad Yani Cimahi, Indonesia
A. M. Maskoen
Oral Biology Department, Faculty of Dentistry, Universitas Padjadjaran / Health Study Unit of Hasan Sadikin Hospital Bandung Indonesia
E. S. S. Soemantri
Orthodontic Department, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia
H. Soedjana
Department of Surgery, Division of Plastic Surgery Reconstruction and Esthetic, Faculty of Medicine, Universitas Padjadjaran Bandung, Indonesia
D. Hilmanto
Department of Pediatric, Faculty of Medicine Universitas Padjadjaran Bandung, Indonesia

Corresponding Author(s) : S. L. Nasroen

kianiun@yahoo.com

Cellular and Molecular Biology, Vol. 63 No. 2: Issue 2

Abstract

Non-syndromic cleft palate only (NS CPO) is one of the most common congenital malformations that affect between 1 in 1000 - 2500 live births worldwide. The etiopathogenesis of clefts including NS CPO has been widely studied but is still poorly understood. NS CPO is considered to be a genetically complex, multifactorial disease. Based on several studies, mutations of TGFβ3 gene emerged as the strong candidate gene associated with NS CPO. The purpose of this study was to analyze the relationship between the TGFβ3 / SfaN1 gene variant and the risk of NS CPO in Indonesian patients. This study was case control design using samples from 31 NS CPO subjects and 35 control subjects. DNA was extracted from venous blood and the segment of TGFβ3 gene/ SfaN1 were amplified by using polymerase chain reaction (PCR) technique, then digestion products by SfaN1 restriction enzyme which can detect locus of gene variant / polymorphism from restriction fragment length polymorphisms (RFLP) method were evaluated. The results indicated that the gene variant as substitution of base G into A was identified in TGFβ3 gene and the frequency of heterozygous mutant GA genotype was 63,6% in NS CPO subjects and 36,4% in control subjects. The frequency of heterozygous mutant GA genotype was associated with increased risk of NS CPO (odds ratio (OR) = 2,260, 95% CI = 0,592 - 8,625). In conclusion, TGFβ3 gene / SfaN1 polymorphism can be considered as the risk factor associated with NS CPO in Indonesian patients.

Keywords

Non syndromic cleft palate only PCR-RFLP TGFβ3 gene SfaN1 Gene variant.
Nasroen, S. L., Tajrin, A., Fauziah, P. N., Maskoen, A. M., Soemantri, E. S. S., Soedjana, H., & Hilmanto, D. (2017). TGFíŸ3 / SfaN1 gene variant and the risk factor of nonsyndromic cleft palate only among Indonesian patients. Cellular and Molecular Biology, 63(2), 88–91. https://doi.org/10.14715/cmb/2017.63.2.13
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References
  1. Wyszynski, DF, Beaty TH, and Maestry NE. Genetics of nonsyndromic oral clefts revisited. Cleft Palate Craniofac J 1996;33: 406-17.
  2. Machida J,Yoshiura K, Funkhauser CD, Natsume N, Kawai T, and Murray JC. Transforming Growth Factor-a (TGFA): Genomic structure, boundary sequences, and mutations analysis in nonsyndromic cleft lip/palate and cleft palate only. Genomics 1999; 61:237-242.
  3. Murray JC, Buetow KH, Weber JL, Ludwigsen S, Scherpbier-Heddema T, Manion F, et al. A comprehensive human linkage map with centimorgan density. Science 1994: 265:2049-54.
  4. Koillinen H. Molecular genetics of non-syndromic cleft palate and van der woude syndrome. Helsinky University Biomedical Dissertation No. 41. 2003
  5. Jugessur A, Farlie PG, Kilpatrick N. The genetics of isolated orofacial clefts: from genotypes to subphenotypes. Oral Dis 2009; 15:437–53.
  6. Iwata J, Parada C, Chai Y. The mechanism of TGF-β signaling during palate development. Oral Dis 2011; 17: 733-44
  7. Lee HK, Kim SS, Son WS. Characteristic of MSX1 gene in Korean nonsyndromic cleft lip and palate individuals. Korean J Orthod 2008;38:133-43
  8. Chai Y, Maxson RE Jr. Recent advances in craniofacial morphogenesis. Dev Dyn. 2006; 235:2353– 75.
  9. Cobourne MT. The complex genetics of cleft lip and palate. Eur J Orthod. 2004; 26:7–16.
  10. Lidral AC, Moreno LM, Bullard SA. Genetic Factors and Orofacial Clefting. Semin Orthod 2008; 14:103–14.
  11. Zhu H, Kartiko S, Finnell RH. Importance of gene-environment interactions in the etiology of selected birth defects. Clin Genet 2009; 75:409–23.
  12. Curtis EJ, Fraser F, Warburton D. Congenital cleft lip and palate. Am J Dis Child 1961; 102:853-57.
  13. Brunet CL, Sharpe PM, Ferguson MW. Inhibition of TGF-beta 3 (but not TGF-beta 1 or TGF-beta 2) activity prevents normal mouse embryonic palate fusion. Int J Dev Biol 1995; 39:345-55
  14. Vieira AR, Orioli IM, Castilla EE, Cooper ME, Marazita ML, Murray JC. MSX1 and TGFB3 contribute to clefting in South America. J Dent Res 2003; 82:289-92
  15. Shaikh S, Ravenndranath R, Banerjee M, Joseph A, Jahgirdar P. Evidence for transforming growth factor–beta 3 gene polymorphism in nonsyndromic cleft lip and palate patients from Indian sub-continent. Med Oral Patol Oral Cir Bucal. 2012; 17:197-200
  16. Kim MH, Kim HJ, Choi JY, Nahm DS. Transforming growth factor–beta 3 gene SfaN1 polymorphism in Korean nonsyndromic cleft lip and palate patients. J Biochem Mol Biol 2003; 36:533-7
  17. Sun D, Vanderburg CR, Odierna GS, Hay ED. TGFbeta3 promotes transformation of chicken palate medial edge epithelium to mesenchyme in vitro. Development 1998; 125:95-105
  18. Taya Y, O'Kane S, Ferguson MW. Pathogenesis of cleft palate in TGF-beta3 knockout mice. Development 1999; 126:3869-79
  19. Suazo J, Santos JL, Scapoli L, Jara L, Blanco R. Association Between TGFB3 and Nonsyndromic Cleft Lip With or Without Cleft Palate in a Chilean Population. Cleft Palate–Craniofac J 2010; 47:513-17
  20. Ulucan K, Bayraktar N, Parmaksiz E, Akcay A, Güney AI. Transforming growth factor-β3 intron 5 polymorphism as a screening marker for non-syndromic cleft lip with or without cleft palate. Mol Med Reports 2012; 6:1465-67,
  21. Ensembl Genome Browser. [download on July 2016] Available from: http://www.ensembl.org/Homo_sapiens
  22. Parada C, Li J, Iwata J, Suzuki A, Chai Y. CTGF Mediates Smad-Dependent Transforming Growth Factor Signaling To Regulate Mesenchymal Cell Proliferation during Palate Development. Mol Cell Bio 2013; 33:3482–93
  23. Tolarová MM, Cervenka J. Classiï¬cation and birth prevalence of orofacial clefts. Am J Med Genet 1998; 75:126–37.
  24. Sun D, Vanderburg CR, Odierna GS, Elizabeth DH. TGFβ3 promotes transformation of chicken palate medial edge epithelium to mesenchyme in vitro. Development 1998; 125: 95-105.
  25. Kaartinen V, Cui XM, Heisterkamp N, Groffen J, Shuler CF. Transforming growth factor-beta3 regulates transdifferentiation of medial edge epithelium during palatal fusion and associated degradation of the basement membrane. Dev Dyn 1997; 209:255–60
  26. Tudela C, Formoso MA, Martí­nez T, Pérez R, Aparicio M, Maestro C, et al. TGF-beta3 is required for the adhesion and intercalation of medial edge epithelial cells during palate fusion. Int J Dev Biol 2002; 46:333-6
  27. Proetzel G, Pawlowski SA, Wiles MV, Yin M, Boivin GP, Howles PN, Ding J, Ferguson MW and Doetschman T: Transforming growth factor-beta 3 is required for secondary palate fusion. Nat Genet 1995; 11: 409-14
  28. Murray JC: Gene/environment causes of cleft lip and/or palate. Clin Genet 2002; 61: 248-56,
  29. Lidral AC, Murray JC, Buetow KH, Basart AM, Schearer H, Shiang R, et al. Studies of the candidate genes TGFB2, MSX1, TGFA, and TGFB3 in the etiology of cleft lip and palate in the Philippines. Cleft Palate Craniofac J 1997; 34:1-6
  30. Jugessur A, Lie RT, Wilcox AJ, Murray JC, Taylor JA, Saugstad OD, et al. Variants of developmental genes (TGFA, TGFB3, and MSX1) and their associations with orofacial clefts: a case-parent triad analysis. Genet Epidemiol 2003; 24:230-9
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