Association between Prostaglandin Receptor Gene Polymorphism and Response to Anti Leukotriene among Children with Bronchial Asthma

Abstract

Background:Bronchial asthma is chronic respiratory diseases (CRDs) are form the most common causes leading to death worldwide, and bronchial asthma is rated the most common chronic disease affecting children. The function of prostaglandin D2 (PGD2) may affect the response of the leukotriene receptor antagonist (LTRA).

Aim of the study: This study aimed to identify PTGDR single nucleotide polymorphism and response to leukotriene receptor antagonist (LTRA).

Patients and methods:This study was a case control study including fifty asthmatic patients (25 males and 25 females. They were classified into 4 subgroups according to GINA, 2016 classification: mild intermittent, mild persistent, moderate persistent and severe persistent. Fifty clinically healthy control participants with matched age and sex were thoroughly evaluated, selected    after careful clinical examination. All patient underwent to full history taking, clinical examination, assessment of pulmonary function (FEV1%, FVC% and PEF %) before and after montelukast (5 mg per day), Total serum IgE level assessment.Detection of SNP (PTGDR)—441T/C (rs803010) after PCR amplification of the target gene In all, 50 subjects with asthma performed an exercise challenge test twice both before and after receiving their daily dose of montelukast (5 mg per day) for 8 weeks.

Results:There were no statistically significant differences between patients and control regarding PTGDR polymorphism, so polymorphism at codon 22q14 can't be considered as a determinant factor for asthma susceptibility. This study revealed a strong positive association between SNPs at codon 22q14 and asthma severity. Patients carrying PTGDR T/C high risk of asthma severity while PTGDR homozygous can be considered as a protective risk factor for severe grades of asthma. patients having PTGDR T/C genotype are significantly responsive to antileukotriene, followed by PTGDR T/T Homozygous, while patients having PTGDR C/C genotype respond poorly to antileukotriene.no significant relationship had been found between PTGDR polymorphism of antileukotriene receptor and elevated levels of neither total serum IgE nor eosinophilic count for all studied genotypes.

Conclusion: Antileukotriene receptor polymorphism at codon 22q14 is not associated with asthma susceptibility; however, it can be a determinant factor for asthma severity and response to antileukotriene in Egyptian asthmatic children, to be confirmed by further Pharmacogenomic studies.