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|Title: ||Screening for Genetic Variants of IL-4 and ADAM33 Genes in a Sample from Asthmatic Saudi Children in Riyadh|
|Authors: ||Khayyat, Arwa Ishaq|
|Keywords: ||Genetic Variants|
Asthmatic Saudi Children
|Issue Date: ||5-Jul-2010 |
|Abstract: ||Asthma is a pulmonary disease characterized by intermittent narrowing of the small airways of the lungs with subsequent reversible airflow obstruction, airway inflammation and bronchial hyper responsiveness (BHR). It is a multifactorial and polygenic disorder, which is induced by a number of genetic and environmental factors, and genetic play a critical role in the development of asthma. Association studies have demonstrated that over 100 variants in candidate genes are associated with asthma in different ethnic group including IL-13, IL-5 IL-4R, IL-4, TNF, NOS1, ADAM33 and ARG2.
This study was designed to identify SNPs linked to asthma development in Saudi asthmatic children. Blood was collected from 107 asthmatic patients attending clinics at King Khalid University Hospital and 87 control subjects. DNA was extracted and three different genotyping techniques: RT-PCR for allele specific discrimination, multiplex ARMS and RFLP, were used to investigate the association between 4 single nucleotide polymorphisms (SNPs) in the ADAM33 gene (T1, T2, ST+4 and S1), and two SNPs in the IL-4 gene(-C590T and –C519T) with asthma development
The difference in the genotype frequencies of T2 and T1 SNPs in asthmatic children compared to controls were statistically significant (p<0.05) and the mutant allele showed association with asthma in Saudi children. The S1 polymorphism in the exon19, and the ST+4 polymorphism in the intron 19 of the ADAM33 gene, were examined in the asthmatic children and controls, no significant differences were identified between the two groups.
The second gene examined during this study was IL-4. Two polymorphism: -590 C>T transition and -519 C>T transition, both in the promoter regions of the IL-4 gene, were investigated. The genotype frequency of -590 C>T polymorphism was not different statistically (p>0.05).
Finally, the last SNP in IL-4 investigated during our investigation was –C 519 T polymorphism which the genotype frequency showed statistically significant difference (p<0.05).
In conclusion, the results of this study showed that the T2 G/A and T1 A/G polymorphisms in the cytoplasmic domain of ADAM33 are significantly associated with asthma development in Saudis. The substitution of G by A in the T2 SNP results in the substitution of Pro with Ser at position 744, in the cytoplasmic domain of the protein and the substitution of A by G in the T1 SNP results in the substitution of Met with Thr at position 764. These could potentially alter intracellular signaling, resulting in increased fibroblast and smooth muscle
proliferation. These results are in agreement to the results reported in US Caucasian and US Hispanic, but are different from the results reported in the Dutch and African American. Meanwhile, the ST+4 and S1 results in Saudis are in agreement with the results reported in Caucasian, US Hispanic, Dutch and African American which showed no significant association with asthma development. In the IL4 genes -590 C>T, the results in Saudis are similar to Hispanic.
There is a need for further association studies in Saudi asthmatic patients to identify markers that can be useful in early detection of asthma. In addition, the sequencing of ADAM33 gene may show novel polymorphisms in the Saudi population.|
|Appears in Collections:||College of Science|
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