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Абстрактный

Single Nucleotide Polymorphism of IL4C-590T and IL4RA 175V and Immunological Parameters in Egyptian Asthmatics with Different Clinical Phenotypes

Magdy Zedan, Ashraf Bakr, Basma Shouman, Hosam Zaghloul, Mohammad Al-Haggar, Mohamed Zedan and Amal Osman

Objectives: Circulating cytokines and genetic patterns may help to discriminate certain asthma phenotypes.

Methods: Eighty two uncontrolled asthmatic children and twenty controls were enrolled in the study. After validation of asthma symptoms, three proposed phenotypes were formed: cough, Shortness Of Breath (SOB), and cough with SOB. Measurement of pulmonary function tests, Fractional Exhaled Nitric Oxide (FENO), eosinophilic percentage, serum levels of total IgE, IL-17 and IL-9 were done. Two Single-Nucleotide Polymorphisms (SNPs) in IL4 and IL4RA were genotyped using PCR-RFLP method.

Results: Regarding SNP IL4RA-175V, cases showed heterozygous AG predominance whereas controls showed more homozygous GG genotype. Cough group showed significant decrease in both FEV1/FVC ratio in comparison to SOB and cough with SOB groups. Also, this group showed strong inverse relationship between FEV1 values and serum IL-9. In addition, there was significant increase in serum levels of IL-17 among homozygous CC compared to CT heterozygous patients of SNP IL-4C 590T in both cough group and SOB group. Cough with SOB group showed significant increase of serum levels of IL-9 when compared to cough group. Also, it showed elevated serum level of IL-9 compared to the other two phenotypes among individuals with IL4RA 175V AA and GG genotypes. SOB group showed higher prevalence of TT genotype of SNP IL-4C 590T in comparison to the cough group.

Conclusions: Our data show diversity in genotyping and cytokine profiles between asthma as a group and the proposed clinical phenotypes. This diversity clarifies the importance of classifying asthma depending on the proposed symptomatology.