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

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.

Keywords

• Hipoksi ile indüklenebilir faktör 1,Yarık dudak,Yarık damak

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

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.

Keywords

• Hypoxia-inducible factor 1,Cleft lip,Cleft palate

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