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

Year 2020, Volume: 4 Issue: 3, 128 - 133, 31.12.2020

Abstract

Objective: 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, atopy, family history as well as asthma severity and asthma control levels in both groups the difference was found to be statistically insignificant.
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.

References

  • Referans1. Masoli M, et al. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004; 59: 469-78
  • Referans2. Chung HL. Asthma in childhood: a complex, heterogeneous disease. Korean J Pediatr 2011; 54:1-5.
  • Referans3. Wojno EDT, et al. The prostaglandin D2 receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung. Mucosal Immunol 2015; 8(6): 1313-23.
  • Referans4. Spik I, et al. Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse. J Immunol 2005; 174(6):3703-8.
  • Referans5. Fajt M., et al. Prostaglandin D2 pathway upregulation: Relation to asthma severity, control, and TH2 inflammation. J Allergy Clin Immunol 2013; 131(6): 1504-12.
  • Referans6. Kagawa S, et al. Role of prostaglandin D2 receptor CRTH2 in sustained eosinophil accumulation in the airways of mice with chronic asthma. Int Arch Allergy Immunol 2011;155 Suppl 1:6-11.
  • Referans7. Hsu SC, et al. Novel SNPs in a candidate gene, CRTH2, for allergic diseases. Genes Immun 2002; 3(2):114-6.
  • Referans8. Huang JL, et al. Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability. Hum Mol Genet 2004;13(21):2691-7.
  • Referans9. Wang J, et al. Genetic variations in chemoattractant receptor expressed on Th2 cells (CRTH2) is associated with asthma susceptibility in Chinese children. Mol Biol Rep 2009; 36(6):1549-53.
  • Referans10. Cameron L, et al. Genetic variation in CRTh2 influences the development of allergic phenotypes. Allergy 2009; 64(10): 1478-85.
  • Referans11. Maeda Y, et al. Genetic impact of functional single nucleotide polymorphisms in the 3'-UTR region of the chemoattractant receptor expressed on Th2 cells (CRTH2) gene on asthma and atopy in a Japanese population. Int Arch Allergy Immunol. 2007; 142(1): 51-8.

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

Year 2020, Volume: 4 Issue: 3, 128 - 133, 31.12.2020

Abstract

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 YÖNTEM: 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, eşlik eden atopi, aile öyküsü, ağırlık derecesi ve astım kontrol düzeyleri karşılaştırıldığında istatistiksel açıdan anlamlı bulunmadı.
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.

References

  • Referans1. Masoli M, et al. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004; 59: 469-78
  • Referans2. Chung HL. Asthma in childhood: a complex, heterogeneous disease. Korean J Pediatr 2011; 54:1-5.
  • Referans3. Wojno EDT, et al. The prostaglandin D2 receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung. Mucosal Immunol 2015; 8(6): 1313-23.
  • Referans4. Spik I, et al. Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse. J Immunol 2005; 174(6):3703-8.
  • Referans5. Fajt M., et al. Prostaglandin D2 pathway upregulation: Relation to asthma severity, control, and TH2 inflammation. J Allergy Clin Immunol 2013; 131(6): 1504-12.
  • Referans6. Kagawa S, et al. Role of prostaglandin D2 receptor CRTH2 in sustained eosinophil accumulation in the airways of mice with chronic asthma. Int Arch Allergy Immunol 2011;155 Suppl 1:6-11.
  • Referans7. Hsu SC, et al. Novel SNPs in a candidate gene, CRTH2, for allergic diseases. Genes Immun 2002; 3(2):114-6.
  • Referans8. Huang JL, et al. Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability. Hum Mol Genet 2004;13(21):2691-7.
  • Referans9. Wang J, et al. Genetic variations in chemoattractant receptor expressed on Th2 cells (CRTH2) is associated with asthma susceptibility in Chinese children. Mol Biol Rep 2009; 36(6):1549-53.
  • Referans10. Cameron L, et al. Genetic variation in CRTh2 influences the development of allergic phenotypes. Allergy 2009; 64(10): 1478-85.
  • Referans11. Maeda Y, et al. Genetic impact of functional single nucleotide polymorphisms in the 3'-UTR region of the chemoattractant receptor expressed on Th2 cells (CRTH2) gene on asthma and atopy in a Japanese population. Int Arch Allergy Immunol. 2007; 142(1): 51-8.
There are 11 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research Article
Authors

Mevlüt Salim This is me 0000-0002-8335-3578

Sinem Güven Önel 0000-0002-6516-460X

Mutlu Yüksek 0000-0002-3835-3149

Publication Date December 31, 2020
Acceptance Date November 26, 2020
Published in Issue Year 2020 Volume: 4 Issue: 3

Cite

Vancouver Salim M, Güven Önel S, Yüksek M. Th2 Üzerinde Eksprese Olan Kemoatraktan Reseptör Homoloğu Gen Polimorfizminin Çocukluk Çağı Atopik Astımındaki Rolü. Med J West Black Sea. 2020;4(3):128-33.

Medical Journal of Western Black Sea is a scientific publication of Zonguldak Bulent Ecevit University Faculty of Medicine.

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This journal is published three annually in April, August and December.
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