Türk popülasyonunda bronkopulmoner displazi insidansı ile ilişkisinin araştırılması için rs3771150 polimorfizminin genotiplenmesi ve analizi

Öz

Amaç: Bu çalışmada Türkiye’de erken doğan bebeklerde görülen BPD insidansı ile IL-18RAP üzerinde bulunan rs3771150 polimorfizmi arasındaki ilişki araştırılmıştır. 

Materyal ve Metod: Bu polimorfizmin alel ve genotip frekansları multipleks reaksiyonlar ve MALDI-TOF kütle spektrometresi yöntemi ile elde edilen genotipleme sonuçları kullanılarak analiz edilmiştir. Buna ek olarak hastalardan elde edilen klinik ve demografik veriler de BPD insidansı ile ilişkileri açısından değerlendirilmiştir. 

Bulgular: Türk popülasyonu için rs3771150 polimorfizminin yabanıl genotipi GG olarak belirlenmiştir (n=49 kontrol, n=46 BPD hastası). Diğer genotipler (AG ve AA) analiz edildiğinde BPD insidansı ile anlamlı bir ilişki kurulamamıştır (p>0.05).

Sonuç: Erken doğan 192 Türk bebekte rs3771150 polimorfizmi ile BPD insidansı arasında anlamlı bir ilişki bulunamamıştır.

Anahtar Kelimeler

• Bronchopulmonary dysplasia,multiplex polymerase chain reaction,single nucleotide polymorphism,SNP genotyping

Genotyping and analysis of rs3771150 polymorphism to investigate an association with bronchopulmonary dysplasia incidence in Turkish population

Öz

Objectives: rs3771150 polymorphism on IL-18RAP was chosen to be investigated in terms of determining a relationship with BPD incidence seen in preterm infants born in Turkey. 

Materials and Method: Allele and genotype frequencies of this polymorphism was analyzed from genotyping results obtained by multiplex reactions and MALDI-TOF mass spectrometry method. In addition, clinical and demographic data obtained from the patients were also inquired in this study to determine any relationship with BPD incidence. 

Results: GG genotype has been determined as the wild type genotype of rs3771150 polymorphism for the Turkish population (n=49 in control group, n=46 in BPD group). When other genotypes (AG and AA) were analyzed no significant relationship was found with BPD incidence (p>0.05).

Conclusion: No significant relationship could be determined between rs3771150 polymorphism and BPD incidence in 192 preterm Turkish infants.

Kaynakça

1. 1. Baraldi E, Carraro S, Filippone M. Bronchopulmonary dysplasia: definitions and long-term respiratory outcome. Early Hum Dev 2009;85(10 Suppl):S1-3.
2. 2. Kotecha S. Lung growth: implications for the newborn infant. Arch Dis Child Fetal Neonatal Ed 2000;82:F69-74.
3. 3. Maeda Y, Davé V, Whitsett JA. Transcriptional control of lung morphogenesis. Physiol Rev 2007;87:219-44.
4. 4. Northway WH Jr, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med 1967;276:357-68.
5. 5. Warburton D, El-Hashash A, Carraro G, Tiozzo C, Sala F, Rogers O, et al. Lung organogenesis. Curr Top Dev Biol 2010;90:73-158.
6. 6. Hashimoto S, Nakano H, Singh G, Katyal S. Expression of Spred and Sprouty in developing rat lung. Mech Dev 2002;119 Suppl 1:S303-9.
7. 7. Lu MM, Li S, Yang H, Morrisey EE. Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues. Mech Dev 2002;119 Suppl 1:S197-202.
8. 8. Balany J, Bhandari V. Understanding the Impact of Infection, Inflammation, and Their Persistence in the Pathogenesis of Bronchopulmonary Dysplasia. Front Med (Lausanne) 2015;2:90.

9. 9. Koç E. Yeni bronkopulmoner displazi. T Klin J Ped 2004;2:396-402.
10. 10. Gardner SL, Carter BS, Hines E, Hernandez JH. Neonatal Intensive Care. 7th ed. St. Louis: Mosby Elsiever; 2011.
11. 11. Eber E, Zach MS. Long term sequelae of bronchopulmonary dysplasia (chronic lung disease of infancy). Thorax 2001;56:317-23.
12. 12. Özkan H, Köksal N, Çetinkaya M, Canıtez Y. Bronkopulmoner displazide risk faktörleri. Güncel Pediatri 2008;6:66-71.
13. 13. Bhandari V, Bizzarro MJ, Shetty A, Zhong X, Page GP, Zhang H, et al. Familial and genetic susceptibility to major neonatal morbidities in preterm twins. Pediatrics 2006;117:1901-6.
14. 14. Lavoie PM, Pham C, Jang KL. Heritability of bronchopulmonary dysplasia, defined according to the consensus statement of the national institutes of health. Pediatrics 2008;122:479-85.
15. 15. Floros J, Londono D, Gordon D, Silveyra P, Diangelo SL, Viscardi RM, et al. IL-18R1 and IL-18RAP SNPs may be associated with bronchopulmonary dysplasia in African-American infants. Pediatr Res 2012;71:107-14.
16. 16. Krueger M, Heinzmann A, Mailaparambil B, Härtel C, Göpel W. Polymorphisms of interleukin 18 in the genetics of preterm birth and bronchopulmonary dysplasia. Arch Dis Child Fetal Neonatal Ed 2011;96:F299-300.
17. 17. Zhernakova A, Festen EM, Franke L, Trynka G, van Diemen CC, Monsuur AJ, et al. Genetic analysis of innate immunity in Crohn's disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP. Am J Hum Genet 2008;82:1202-10.
18. 18. Hirota T, Takahashi A, Kubo M, Tsunoda T, Tomita K, Sakashita M, et al. Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat Genet 2012;44:1222-6.
19. 19. Liu H, Irwanto A, Tian H, Fu X, Yu Y, Yu G, et al. Identification of IL18RAP/IL18R1 and IL12B as leprosy risk genes demonstrates shared pathogenesis between inflammation and infectious diseases. Am J Hum Genet 2012;91:935-41.
20. 20. Hunt KA, Zhernakova A, Turner G, Heap GA, Franke L, Bruinenberg M, et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet 2008;40:395-402.
21. 21. Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 2008;359:2767-77.
22. 22. Sequenom, iPLEXTM Gold Application Guide. November 10, 2006
23. 23. QIAamp® DNA Mini and Blood Mini HandBook. 5th ed. Qiagen; 2016.
24. 24. Sambrook J. Fritsch EF, Maniatis T. Molecular cloning: A laboratory manual. 2nd ed. New York: John Wiley & Sons; 1989.