Sendromik olmayan obez hastalarda yeni nesil dizi analizi ile uridin difosfat glukronil transferaz 1A1 (UGT1A1) geninin araştırılması
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Dosyalar
Tarih
2019
Yazarlar
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Yayıncı
Düzce Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Obezite dünya genelinde artan prevelansı ve özellikle gelişmiş ülkelerde en önemli sağlık sorunlarından biridir. Bildiğimiz kadarıyla literatürde UGT1A1 geninin non sendromik obezlerde yeni nesil dizi analizi yöntemi ile değerlendirildiği çalışma yoktur. Bu çalışma ile Düzce Üniversitesi Hastanesi Çocuk Polikliniklerine obezite tanısıyla başvuran olgularda yeni nesil dizi analizi ile UGT1A1 genindeki değişimleri ortaya koymayı amaçladık. Materyel metod: Olguların hedeflenen moleküler genetik tanısı için ilk olarak rutin amaçlı istenilen tam kan örneklerinden geriye kalan atık kanlardan DNA izolasyon işlemi yapıldı ve hedefe yönelik yeni nesil dizi analizi yöntemiyle moleküler genetik analizi yapıldı Bulgular: Çalışmaya 45 obez (%76,3), 14 kontrol (%23,7) dahil edildi. UGT1A1 gen değişimi açısından Obez çocukların 28'inde (%62) genetik değişim varken kontrol grubunda genetik değişim 7'sinde (%50) idi (p>0.05). Kontrol grubunda sadece 2 varyasyon saptanmışken, obez grubunda bu varyasyona ek 7 varyasyon daha saptandı. Obezite başlangıç yaşının 2 yaş altında ve üstünde oluşmasına göre sınıflandırdığımızda ilk 2 yıl içinde (erken başlangıçlı) olan hastaların %38,9'unda, 2 yaş sonrası herhangi bir yaşta (geç başlangıçlı) obezite kliniği gelişen hastaların %77,8'inde UGT1A1 geninde varyasyon oluştuğunu gözlemledik. 2 yaş altında obezite gelişen çocuklarda hem total hem direk bilirubin seviyesinin anlamlı olarak daha düşük saptandı. Sonuç: Geç başlangıçlı grupta UGT1A1 geninde oluşmuş olan genetik değişimler lojistik regresyon analizi ile değerlendirildiğinde obezitenin geç yaşta olma riskini 3 kat (3,42 %95 CI, 0,15-5,11: p 0,000) oranında arttırdığını gösterdik. Ancak bilirubinin koruyucu etkisi göz önüne alındığında erken başlanıçlı obezitede bilirubinin daha düşük saptanması nedeniyle takiplerinin daha dikkatli yapılması gerekmektedir. Çalışmamız obezite başlangıç yaşı, UGT1A1 gen poliformizmi çeşitliği ve bilirubin seviyesinin yaş bağımlı değişimini gösteren ilk çalışmadır.
Aim: Obesity prevalence is increasing worldwide and it is one of the most important health problems especially in developed countries. To the best of our knowledge, there are no studies in the literature which the UGT1A1 gene has been evaluated by the next generation sequence analysis method in non-syndromic obese patients.In this study, we aimed to determine the changes in the UGT1A1 gene by next generation sequence analysis in patients admitted to the Pediatric Polyclinics of Düzce University Hospital with the diagnosis of obesity. Methods: For the targeted molecular genetic diagnosis of the cases, DNAs isolated from the remaining waste blood which were obtained from whole blood samples for routine purposes and molecular genetic analysis was performed by using targeted next generation sequence analysis method. Results: Forty-five obese patients (76.3%) and 14 controls (23.7%) were included in the study.In terms of genetic changing in UGT1A1 gene, while 28 (62%) of the obese children had genetic changes, there were a genetic changes in 7 (50%) of the control group (p> 0.05). While only 2 genetic variations were detected in the control group, 7 additional variations were detected in the obese group. After classifying according to onset age of obesity (below and over the age of 2 years), we observed that 38.9% of the patients with early onset obesity and 77.8% of the patients with late onset obesity (at any age over 2 years of age) had UGT1A1 gene variations. Both total and direct bilirubin levels were significantly lower in children with obesity under 2 years of age. Conclusion: In the late-onset group, the genetic changes in the UGT1A1 gene were evaluated by logistic regression analysis and we showed that these genetic changes increased the risk of late onset obesity 3 times (3.42 % 95 CI, 0.15-5.11 p: 0.000). However, considering the protective effect of bilirubin, especially for early-onset obesity, follow-up should be performed more carefully because of lower levels of bilirubin. Our study is the first study showing age-related changes between the diversity of UGT1A1 gene polymorphisms, bilirubin levels and onset age of obesity.
Aim: Obesity prevalence is increasing worldwide and it is one of the most important health problems especially in developed countries. To the best of our knowledge, there are no studies in the literature which the UGT1A1 gene has been evaluated by the next generation sequence analysis method in non-syndromic obese patients.In this study, we aimed to determine the changes in the UGT1A1 gene by next generation sequence analysis in patients admitted to the Pediatric Polyclinics of Düzce University Hospital with the diagnosis of obesity. Methods: For the targeted molecular genetic diagnosis of the cases, DNAs isolated from the remaining waste blood which were obtained from whole blood samples for routine purposes and molecular genetic analysis was performed by using targeted next generation sequence analysis method. Results: Forty-five obese patients (76.3%) and 14 controls (23.7%) were included in the study.In terms of genetic changing in UGT1A1 gene, while 28 (62%) of the obese children had genetic changes, there were a genetic changes in 7 (50%) of the control group (p> 0.05). While only 2 genetic variations were detected in the control group, 7 additional variations were detected in the obese group. After classifying according to onset age of obesity (below and over the age of 2 years), we observed that 38.9% of the patients with early onset obesity and 77.8% of the patients with late onset obesity (at any age over 2 years of age) had UGT1A1 gene variations. Both total and direct bilirubin levels were significantly lower in children with obesity under 2 years of age. Conclusion: In the late-onset group, the genetic changes in the UGT1A1 gene were evaluated by logistic regression analysis and we showed that these genetic changes increased the risk of late onset obesity 3 times (3.42 % 95 CI, 0.15-5.11 p: 0.000). However, considering the protective effect of bilirubin, especially for early-onset obesity, follow-up should be performed more carefully because of lower levels of bilirubin. Our study is the first study showing age-related changes between the diversity of UGT1A1 gene polymorphisms, bilirubin levels and onset age of obesity.
Açıklama
YÖK Tez No: 621451
Anahtar Kelimeler
Çocuk Sağlığı ve Hastalıkları, Child Health and Diseases
