Yıl 2020, Cilt 4 , Sayı 4, Sayfalar 285 - 288 2020-04-01

A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother
Yarık damak ve dudaklı çocuklar ve annlerinde HIF1A’nın iki polimorfizminin vaka kontrol çalışması

İbrahim YILDIRIM [1] , Nadir KOÇAK [2] , Kağan KAMAŞAK [3]


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.
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.
  • 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.
Birincil Dil en
Konular Tıp
Bölüm Araştırma makalesi
Yazarlar

Orcid: 0000-0001-5518-5004
Yazar: İbrahim YILDIRIM (Sorumlu Yazar)
Kurum: DICLE UNIVERSITY
Ülke: Turkey


Orcid: 0000-0002-1727-1582
Yazar: Nadir KOÇAK
Kurum: SELÇUK ÜNİVERSİTESİ, TIP FAKÜLTESİ
Ülke: Turkey


Orcid: 0000-0002-0404-9667
Yazar: Kağan KAMAŞAK
Kurum: SİVAS NUMUNE HASTANESİ
Ülke: Turkey


Tarihler

Yayımlanma Tarihi : 1 Nisan 2020

Bibtex @araştırma makalesi { josam715142, journal = {Journal of Surgery and Medicine}, issn = {}, eissn = {2602-2079}, address = {jsurgmed@gmail.com}, publisher = {Fatih BAŞAK}, year = {2020}, volume = {4}, pages = {285 - 288}, doi = {10.28982/josam.715142}, title = {A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother}, key = {cite}, author = {Yıldırım, İbrahim and Koçak, Nadir and Kamaşak, Kağan} }
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 . DOI: 10.28982/josam.715142
MLA 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" . Journal of Surgery and Medicine 4 (2020 ): 285-288 <https://jsurgmed.com/tr/pub/issue/53710/715142>
Chicago 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". Journal of Surgery and Medicine 4 (2020 ): 285-288
RIS TY - JOUR T1 - A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother AU - İbrahim Yıldırım , Nadir Koçak , Kağan Kamaşak Y1 - 2020 PY - 2020 N1 - doi: 10.28982/josam.715142 DO - 10.28982/josam.715142 T2 - Journal of Surgery and Medicine JF - Journal JO - JOR SP - 285 EP - 288 VL - 4 IS - 4 SN - -2602-2079 M3 - doi: 10.28982/josam.715142 UR - https://doi.org/10.28982/josam.715142 Y2 - 2020 ER -
EndNote %0 Journal of Surgery and Medicine A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother %A İbrahim Yıldırım , Nadir Koçak , Kağan Kamaşak %T A case-control study of two polymorphisms of HIF1A in children with cleft lip/palate and in their mother %D 2020 %J Journal of Surgery and Medicine %P -2602-2079 %V 4 %N 4 %R doi: 10.28982/josam.715142 %U 10.28982/josam.715142
ISNAD Yıldırım, İbrahim , Koçak, Nadir , Kamaşak, Kağan . "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 (Nisan 2020): 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. 2020; 4(4): 285-288.
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. Journal of Surgery and Medicine. 2020; 4(4): 285-288.
IEEE İ. Yıldırım , N. Koçak ve K. 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, c. 4, sayı. 4, ss. 285-288, Nis. 2020, doi:10.28982/josam.715142