Mevlüt SALİM, Sinem GÜVEN ÖNEL, Mutlu YÜKSEK

Th2 Üzerinde Eksprese Olan Kemoatraktan Reseptör Homoloğu Gen Polimorfizminin Çocukluk Çağı Atopik Astımındaki Rolü

Amaç: Atopik hastalıkların patogenezinde önemli yeri olan sitokinlerin sekresyonunda, Th2 üzerinde eksprese olan kemoatraktan reseptör homoloğu (TEKRH) (chemoattractant receptor homologous molecule expressed on Th2 - CRTH2) gibi prostaglandin reseptörünün ekspresyonu kritik öneme sahiptir. Çalışmamızda Türk çocuklarındaki astım ile TEKRH gen (G1544C, A1651G) polimorfizmi arasındaki ilişki ve olası tedavi olasılıklarının değerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: Zonguldak BEÜN Sağlık Uygulama ve Araştırma Hastanesi Çocuk Alerji ve İmmünoloji polikliniğine başvuran, 2-16 yaş arası astım hastası 143 çocuk çalışma; 16-55 yaş arası alerjik yakınması ve ailesel öyküsü olmayan 100 sağlıklı yetişkin kontrol grubu olarak belirlendi. Gruplar TEKRH gen (G1544C, A1651G) polimorfizmi açısından incelendi. Periferik kandan alınan örnekler Magrev® Whole Blood Genomic DNA Extraction Kiti kullanılarak yapılan izolasyonu takiben DNA dizi analizi yöntemi kullanıldı. Bulgular: Çalışma ve kontrol gruplarının ortalama yaşları sırasıyla 8±3,5 ve 30±6,9 yıldı. Hastaların TEKRH G1544C gen polimorfizmleri incelendiğinde 48’inin (%33,6) C/G, 13’ünün (%9.1)C/C, 82’sinin (%57.3) G/G; A1651G gen polimorfizminin açısından bakıldığında 45’inin G/A(%31,5), 6’sının (%4,2) G/G ve 92’sinin (%64,3) A/A genotipinde olduğu saptandı. Kontrol grubu G1544C polimorfizmi için değerlendirildiğinde 44’ünün (%44) C/G, 11’inin (%11) C/C ve 45’inin G/G; A1651G gen polimorfizmi açısından 26’sının (%26) G/A, 3’ünün (%3) G/G ve 71’inin(%71) A/A genotipinde olduğu saptandı. Grupların, genotip frekansları, aile öyküsü, ağırlık derecesi ve astım kontrol düzeyleri karşılaştırıldığında istatistiksel açıdan anlamlı bulunmadı. Gruplar arasında tek fark eşlik eden atopinin TERKH G1544C GG polimorfizminde daha sık görülmesi olarak saptandı. Sonuç: Gruplar arasında TEKRH gen polimorfizmi açısından fark saptanmamıştır. Sonuçlar Türk çocuklarında TEKRH gen polimorfizmlerinin astıma yatkınlık açısından risk faktörü taşımadığını düşündürmektedir. Çalışma bize, son dönemde geliştirilen tedavide kullanılabileceği belirtilen TEKRH antagonistlerinin Türk çocukları için uygun tedavi seçeneği olduğuna ilişkin güçlü bilimsel kanıtlar sunmamaktadır.

The Role of Chemoattractant Receptor Homologous Molecule Expressed On Th2 Gene Polymorphism in the Childhood Age Atopic Asthma

Aim: In the secretion of cytokines, which have an important role in the pathogenesis of atopic diseases, the expression of the prostaglandin receptor, such as the chemoattractant receptor homologous molecule expressed on Th2 - (CRTH2), is critical. In our study, it was aimed to evaluate the relationship between asthma and CRTH2 gene (G1544C, A1651G) polymorphism in Turkish children and treatment possibilities with CRTH2 antagonists. Material and Methods: A group of 143 children, between the ages of 2-16 with asthma, who applied to the Zonguldak BEÜN Faculty of Medicine Hospital Pediatric Allergy and Immunology outpatient clinic designated as a study group, and 100 healthy adults without a history of atopy as a control group. Both groups were analyzed for the CRTH2 gene (G1544C, A1651G) polymorphism. Blood samples were taken from both groups, and their DNA was isolated and stored at -20 ° C cabinet. DNA isolation was done using Magrev® Whole Blood Genomic DNA Extraction Kit and DNA sequence analysis method following DNA isolation from peripheral blood. Results: The study and control groups consisted of 143 patients (82 males/61 females) and 100 participants (36 males/64 females), with a mean age of 8±3,5 and 30 ± 6,9 years, respectively. When the results of CRTH2 G1544C gene polymorphism of the patients in the patient group were examined; 48 (%33,6) patients were heterozygous (C/G), 13 (%9,1) were homozygous (C/C) and 82 (%57,3) patients were normal (G/G) genotype. The results for CRTH2 A1651G gene polymorphism of the patient group are examined; 45 (%31,5) patients were heterozygous (G/A), 6 (%4,2) patients were homozygous (G/G) and 92 (%64,3) patients were normal (A/A) genotype. When the control group was evaluated for CRTH2 G1544C polymorphism, 44 (%44) cases were heterozygous (C/G), 11 (%11) were homozygous (C/C) and 45 (%45) cases were normal (G/G) genotype. The results of the CRTH2 A1651G gene polymorphism were examined in the control group, normal (A/A) genotype was detected in 71 (%71) cases, heterozygous (G/A) 26 (%26) and homozygous (G/G) was 3 (%3) cases. Individuals in both groups were compared, there was no statistically significant difference in gene polymorphism, allele distribution,family history as well as asthma severity and asthma control levels in both groups the difference was found to be statistically insignificant. The only statistical difference between the groups was that accompanying atopy was more common in CRTH2 G1544C GG polymorphism. Conclusion: There was no difference between the groups in terms of CRTH2 gene polymorphism. These results suggest that CRTH2 gene polymorphisms are not a strong effect on the pathogenesis of allergic asthma and genetic risk factor susceptibility to asthma in Turkish children. Also, the results of our study did not provide us strong scientific evidence that CRTH2 antagonist drugs, which have been tried to be developed for asthma therapy, would not be a suitable treatment option for Turkish children. However, we consider, studies which are also included in cytokines are needed to better understand the relation between CRTH2 and asthma with larger groups.

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