Research Article
BibTex RIS Cite

Yarık damak ve dudaklı çocuklar ve annlerinde HIF1A’nın iki polimorfizminin vaka kontrol çalışması

Year 2020, Volume: 4 Issue: 4, 285 - 288, 01.04.2020
https://doi.org/10.28982/josam.715142

Abstract

Amaç: Palatogenez, fetal yaşamın erken evrelerinde ortaya çıkan metabolik bir olaydır. Raporlar, hipoksinin damak oluşumunda ve yükselmesinde ve ayrıca dudakların füzyonunda kritik bir durum olduğunu göstermektedir. Çevresel faktörlerin yanı sıra, genetik faktörlerin hipokside önemli rol oynadığı bilinmektedir. Hücrelerin hipoksiye yol açan oksijen basıncındaki değişikliklere cevap verebilme yeteneği, hipoksi ile indüklenebilir faktörler (HIF'ler) olarak bilinen bir transkripsiyon faktörü ailesinin aktivasyonuna bağlıdır. Bu çalışma, yarık dudak/damaklı çocuklar ve bu çocukların annelerinde hipoksi ile indüklenebilir faktör 1, alfa alt birimi (HIF1A)'nin iki polimorfizminin dağılımını belirlemek için yapılmıştır.
Yöntemler: HIF1A'nın (Pro582Ser ve Ala588Thr) iki polimorfik yapısı, çalışma grubu olan yarık dudak/damaklı çocuklar ve annelerinde ve kontrol grubu çocuklar ve annelerinde polimeraz zincir reaksiyonu fragment uzunluğu polimorfizmi (PCR-RFLP) yöntemi kullanılarak incelendi. DNA fragmentleri, kesim işleminden sonar agaroz jelde görüntülendi.
Bulgular: Polimorfik yapılardan Ala588Thr karşılaştırmasında, yarık dudak/damaklı çocuklar ve anneler ile kontrol grubu çocuklar ve anneleri arasında fark gözlenmemiştir. Pro582Ser karşılaştırmasında ise; anne ve çocuk genotiplerinin kontrol gruplarıyla karşılaştırılmasında farklılıklar görülmüştür (P=0.034 ve P=0.023, sırasıyla). Alell karşılaştırmalarında, yarık dudak/damaklı çocukların anneleri ile kontrol grubu anneleri arasında fark gözlenmiştir (P=0.001). Çocuklardaki allel karşılaştırmalarında da, annelerdeki kadar yüksek olmasa da fark görülmüştür (P=0.026).
Sonuç: HIF1A proteinindeki Prolin aminoasitlerinin değişimine neden polimorfizmler, HIF1A proteininin aktivitesini veya ömrünü etkiliyor ve yarık dudak/damak oluşunda rol alıyor olabilir.

References

  • 1. Rajion ZA, Alwi Z. Genetics of cleft lip and palate: a review. Malays J Med Sci. 2007;14(1):4-9.
  • 2. Bekecioğlu M, Türkmen A. Konjenital Yarık Damak ve Dudak Anomalileri [Congenital Cleft Lip-Cleft Palate Anomalies. Turkiye Klinikleri J E N T-Special Topics. 2011;4(3):43-7.
  • 3. Murray JC. Gene/environment causes of cleft lip and/or palate. Clin Genet. 2002;61(4):248-56. doi:10.1034/j.1399-0004.2002.610402.x.
  • 4. Lidral AC, Murray JC, Buetow KH, Basart AM, Schearer H, Shiang R, et al. Studies of the candidates genes TGFB2, MSX1, TGFA, and TGFB3 in the etiology of cleft lip and palate in the Phillipines. Cleft Palate Craniofac J. 1997;34(a):1-6. doi: 10.1597/1545-1569_1997_034_0001_sotcgt_2.3.co_2.
  • 5. Passos-Bueno MR, Gaspar DA, Kamiya T, Tescarollo G, Rabanea D, Richieri-Costa A, et al. Transforming growth factor-alpha and non-syndromic cleft lip with or without palate in Brazilian patients: results of large case-control study. Cleft Palate Craniofac J. 2004;41(4):387–91. doi: 10.1597/03-054.1
  • 6. Tanabe A, Taketani S, Endo-Ichikawa Y, Tokunaga R, Ogawa Y, Hiramoto M. Analysis of the candidate genes responsible for non-syndromic cleft lip and palate in Japanese people. Clin Sci (Lond). 2000;99(2):105-11. doi: 10.1042/cs0990105.
  • 7. Moxham BJ. The development of the palate-a brief review. Eur J Anat. 2003;7 Suppl. (1):53-74.
  • 8. Ferguson MW. Palate development. Development. 1988;103: Suppl:41-60.
  • 9. Singh GD, Moxham BJ, Langley MS, Embery G. Glycosaminoglycan biosynthesis during 5-fluoro-2-deoxyuridine-induced palatal clefts in the rat. Arch Oral Biol. 1997;42(5):355–63. doi: 10.1016/S0003-9969(97)00031-9.
  • 10. Gao F, Okunieff P, Han Z, Ding I, Wang L, Liu W, et al. Hypoxia-induced alterations in hyaluronan and hyaluronidase. Adv Exp Med Biol. 2005;566:249-56. doi: 10.1007/0-387-26206-7_33.
  • 11. Papakonstantinou E, Roth M, Tamm M, Eickelberg O, Perruchould AP, Karakiulakis G. Hypoxia differentially enhances the effects of transforming growth factor-beta isoforms on the synthesis and secretion of glycosaminoglycans by human lung fibroblasts. J Pharmacol Exp Ther. 2002;301(3):830-7. doi: 10.1124/jpet.301.3.830.
  • 12. Park JY, Park JW, Suh SI, Baek WK. D-glucosamine down-regulates HIF-1alpha through inhibition of protein translation in DU145 prostate cancer cells. Biochem Biophys Res Commun. 2009;382(1):96-101. doi: 10.1016/j.bbrc.2009.02.129.
  • 13. Tanimoto K, Yoshiga K, Eguchi H, Kaneyasu M, Ukon K, Kumazaki T, et al. Hypoxia-inducible factor-1αpolymorphisms associated with enhanced transactivation capacity, imlpying clinical significance. Carcinogenesis. 2003;24(11):1779-83. doi: 10.1093/carcin/bgg132.
  • 14. Kim W, Kaelin WG Jr. The von Hippel-Lindau tumor suppressor protein: new insights into oxygen sensing and cancer. Curr Opin Genet Dev. 2003;13(1):55–60. doi: 10.1016/S0959-437X(02)00010-2.
  • 15. Fransén K, Fenech M, Fredrikson M, Dabrosin C, Söderkvist P. Association between ulcerative growth and hypoxia inducible factor-1α polymorphisms in colorectal cancer patients. Mol Carcinog. 2006;45(11):833-40. doi: 10.1002/mc.20209.
  • 16. Kosowski TR, Weathers WM, Wolfswinkel EM, Ridgway EB. Cleft Palate. Semin Plast Surg. 2012;26(4):164-9. doi: 10.1055/s-0033-1333883.
  • 17. Çıldır SK, Çalışkan S, Sandallı N. Dudak-Damak Yarıklarında Etiyoloji, Embriyoloji, Klinik Bulgular ve Tedavi [Etiology, Embryology, Clinical Findings and Treatment of Cleft Lip and Palate]. Ondokuz Mayıs Üniversitesi Diş Hekimliği Fakültesi Dergisi. 2010;11(3):103-8.
  • 18. Kelly D, O’Dowd T, Reulbach U. Use of folic acid supplements and risk of cleft lip and palate in infants: a population-based cohort study. Br J Gen Pract. 2012;62(600):e466-e472. doi: 10.3399/bjgp12X652328.
  • 19. Hiraoka M, Kagawa Y. Genetic polymorphisms and folate status. Congenit Anom (Kyoto). 2017;57(5):142-9. doi: 10.1111/cga.12232.
  • 20. Alfarra HY, Alfarra SR, Sadiq MF. Neural tube defects between folate metabolism and genetics. Indian J Hum Genet. 2011;17(3):126-31. doi: 10.4103/0971-6866.92082
  • 21. Kumar H, Choi DK. Hypoxia Inducible Factor Pathway and Physiological Adaptation: A Cell Survival Pathway? Mediators Inflamm. 2015;2015:584758. doi: 10.1155/2015/584758.
  • 22. Smaldone MC, Maranchie JK. Clinical implications of hypoxia inducible factor in renal cell carcinoma. Urol Onc. 2009;27(3):238-45. doi: 10.1016/j.urolonc.2007.12.001.
  • 23. Millicovsky G, Johnston MC. Hyperoxia and hypoxia in pregnancy: simple experimental manipulation alters the incidence of cleft lip and palate in CL/Fr mice. Proc Natl Acad Sci USA. 1981;78(9):5722-3.

A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother

Year 2020, Volume: 4 Issue: 4, 285 - 288, 01.04.2020
https://doi.org/10.28982/josam.715142

Abstract

Aim: Palatogenesis is a metabolic event that occurs in the initial stages of fetal life. Reports indicate that hypoxia is a critical condition in the formation and elevation of the palate and fusion of the lips. It is known that both environmental and genetic factors play important roles in hypoxia. The ability of the cells to respond to changes in the oxygen pressure that lead to hypoxia depends on the activation of a transcription factor family known as hypoxia-inducible factors (HIFs). This study was conducted to determine the distribution of two polymorphisms of hypoxia-inducible factor 1, alpha subunit (HIF1A) in children with cleft lip/palate and their mothers.
Methods: Two polymorphic structures of HIF1A (Pro582Ser and Ala588Thr) were studied in children with cleft lip/palate and their mothers along with control group children and mothers using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. DNA fragments were monitored by agarose gel electrophoresis after cleavage.
Results: In Ala588Thr comparison, no difference was observed between mothers, children, and their controls. Regarding Pro582Ser, there were differences in the comparison of maternal and children genotypes with control groups (P=0.034 and P=0.023, respectively). In allelic comparisons, there was a difference between mothers of children with cleft lip/palates and the control group (P=0.001). Although this was different in children, it was not as high as in mothers (P=0.026).
Conclusion: HIF1A polymorphisms that change the proline residues may affect the activity or lifespan of HIF1A protein and play a role in the formation of cleft lip/palate.

References

  • 1. Rajion ZA, Alwi Z. Genetics of cleft lip and palate: a review. Malays J Med Sci. 2007;14(1):4-9.
  • 2. Bekecioğlu M, Türkmen A. Konjenital Yarık Damak ve Dudak Anomalileri [Congenital Cleft Lip-Cleft Palate Anomalies. Turkiye Klinikleri J E N T-Special Topics. 2011;4(3):43-7.
  • 3. Murray JC. Gene/environment causes of cleft lip and/or palate. Clin Genet. 2002;61(4):248-56. doi:10.1034/j.1399-0004.2002.610402.x.
  • 4. Lidral AC, Murray JC, Buetow KH, Basart AM, Schearer H, Shiang R, et al. Studies of the candidates genes TGFB2, MSX1, TGFA, and TGFB3 in the etiology of cleft lip and palate in the Phillipines. Cleft Palate Craniofac J. 1997;34(a):1-6. doi: 10.1597/1545-1569_1997_034_0001_sotcgt_2.3.co_2.
  • 5. Passos-Bueno MR, Gaspar DA, Kamiya T, Tescarollo G, Rabanea D, Richieri-Costa A, et al. Transforming growth factor-alpha and non-syndromic cleft lip with or without palate in Brazilian patients: results of large case-control study. Cleft Palate Craniofac J. 2004;41(4):387–91. doi: 10.1597/03-054.1
  • 6. Tanabe A, Taketani S, Endo-Ichikawa Y, Tokunaga R, Ogawa Y, Hiramoto M. Analysis of the candidate genes responsible for non-syndromic cleft lip and palate in Japanese people. Clin Sci (Lond). 2000;99(2):105-11. doi: 10.1042/cs0990105.
  • 7. Moxham BJ. The development of the palate-a brief review. Eur J Anat. 2003;7 Suppl. (1):53-74.
  • 8. Ferguson MW. Palate development. Development. 1988;103: Suppl:41-60.
  • 9. Singh GD, Moxham BJ, Langley MS, Embery G. Glycosaminoglycan biosynthesis during 5-fluoro-2-deoxyuridine-induced palatal clefts in the rat. Arch Oral Biol. 1997;42(5):355–63. doi: 10.1016/S0003-9969(97)00031-9.
  • 10. Gao F, Okunieff P, Han Z, Ding I, Wang L, Liu W, et al. Hypoxia-induced alterations in hyaluronan and hyaluronidase. Adv Exp Med Biol. 2005;566:249-56. doi: 10.1007/0-387-26206-7_33.
  • 11. Papakonstantinou E, Roth M, Tamm M, Eickelberg O, Perruchould AP, Karakiulakis G. Hypoxia differentially enhances the effects of transforming growth factor-beta isoforms on the synthesis and secretion of glycosaminoglycans by human lung fibroblasts. J Pharmacol Exp Ther. 2002;301(3):830-7. doi: 10.1124/jpet.301.3.830.
  • 12. Park JY, Park JW, Suh SI, Baek WK. D-glucosamine down-regulates HIF-1alpha through inhibition of protein translation in DU145 prostate cancer cells. Biochem Biophys Res Commun. 2009;382(1):96-101. doi: 10.1016/j.bbrc.2009.02.129.
  • 13. Tanimoto K, Yoshiga K, Eguchi H, Kaneyasu M, Ukon K, Kumazaki T, et al. Hypoxia-inducible factor-1αpolymorphisms associated with enhanced transactivation capacity, imlpying clinical significance. Carcinogenesis. 2003;24(11):1779-83. doi: 10.1093/carcin/bgg132.
  • 14. Kim W, Kaelin WG Jr. The von Hippel-Lindau tumor suppressor protein: new insights into oxygen sensing and cancer. Curr Opin Genet Dev. 2003;13(1):55–60. doi: 10.1016/S0959-437X(02)00010-2.
  • 15. Fransén K, Fenech M, Fredrikson M, Dabrosin C, Söderkvist P. Association between ulcerative growth and hypoxia inducible factor-1α polymorphisms in colorectal cancer patients. Mol Carcinog. 2006;45(11):833-40. doi: 10.1002/mc.20209.
  • 16. Kosowski TR, Weathers WM, Wolfswinkel EM, Ridgway EB. Cleft Palate. Semin Plast Surg. 2012;26(4):164-9. doi: 10.1055/s-0033-1333883.
  • 17. Çıldır SK, Çalışkan S, Sandallı N. Dudak-Damak Yarıklarında Etiyoloji, Embriyoloji, Klinik Bulgular ve Tedavi [Etiology, Embryology, Clinical Findings and Treatment of Cleft Lip and Palate]. Ondokuz Mayıs Üniversitesi Diş Hekimliği Fakültesi Dergisi. 2010;11(3):103-8.
  • 18. Kelly D, O’Dowd T, Reulbach U. Use of folic acid supplements and risk of cleft lip and palate in infants: a population-based cohort study. Br J Gen Pract. 2012;62(600):e466-e472. doi: 10.3399/bjgp12X652328.
  • 19. Hiraoka M, Kagawa Y. Genetic polymorphisms and folate status. Congenit Anom (Kyoto). 2017;57(5):142-9. doi: 10.1111/cga.12232.
  • 20. Alfarra HY, Alfarra SR, Sadiq MF. Neural tube defects between folate metabolism and genetics. Indian J Hum Genet. 2011;17(3):126-31. doi: 10.4103/0971-6866.92082
  • 21. Kumar H, Choi DK. Hypoxia Inducible Factor Pathway and Physiological Adaptation: A Cell Survival Pathway? Mediators Inflamm. 2015;2015:584758. doi: 10.1155/2015/584758.
  • 22. Smaldone MC, Maranchie JK. Clinical implications of hypoxia inducible factor in renal cell carcinoma. Urol Onc. 2009;27(3):238-45. doi: 10.1016/j.urolonc.2007.12.001.
  • 23. Millicovsky G, Johnston MC. Hyperoxia and hypoxia in pregnancy: simple experimental manipulation alters the incidence of cleft lip and palate in CL/Fr mice. Proc Natl Acad Sci USA. 1981;78(9):5722-3.
There are 23 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research article
Authors

İbrahim Yıldırım 0000-0001-5518-5004

Nadir Koçak 0000-0002-1727-1582

Kağan Kamaşak 0000-0002-0404-9667

Publication Date April 1, 2020
Published in Issue Year 2020 Volume: 4 Issue: 4

Cite

APA Yıldırım, İ., Koçak, N., & Kamaşak, K. (2020). A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother. Journal of Surgery and Medicine, 4(4), 285-288. https://doi.org/10.28982/josam.715142
AMA Yıldırım İ, Koçak N, Kamaşak K. A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother. J Surg Med. April 2020;4(4):285-288. doi:10.28982/josam.715142
Chicago Yıldırım, İbrahim, Nadir Koçak, and Kağan Kamaşak. “A Case-Control Study of Two Polymorphisms of HIF1A in Children With Cleft lip/Palate and in Their Mother”. Journal of Surgery and Medicine 4, no. 4 (April 2020): 285-88. https://doi.org/10.28982/josam.715142.
EndNote Yıldırım İ, Koçak N, Kamaşak K (April 1, 2020) A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother. Journal of Surgery and Medicine 4 4 285–288.
IEEE İ. Yıldırım, N. Koçak, and K. Kamaşak, “A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother”, J Surg Med, vol. 4, no. 4, pp. 285–288, 2020, doi: 10.28982/josam.715142.
ISNAD Yıldırım, İbrahim et al. “A Case-Control Study of Two Polymorphisms of HIF1A in Children With Cleft lip/Palate and in Their Mother”. Journal of Surgery and Medicine 4/4 (April 2020), 285-288. https://doi.org/10.28982/josam.715142.
JAMA Yıldırım İ, Koçak N, Kamaşak K. A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother. J Surg Med. 2020;4:285–288.
MLA Yıldırım, İbrahim et al. “A Case-Control Study of Two Polymorphisms of HIF1A in Children With Cleft lip/Palate and in Their Mother”. Journal of Surgery and Medicine, vol. 4, no. 4, 2020, pp. 285-8, doi:10.28982/josam.715142.
Vancouver Yıldırım İ, Koçak N, Kamaşak K. A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother. J Surg Med. 2020;4(4):285-8.