T1 and T2 ADAM33 single nucleotide polymorphisms and the risk of childhood asthma in a Saudi Arabian population: a pilot study

Arwa Ishaq Al-Khayyat, Mohammed Al-Anazi, Arjumand Warsy, Alejandro Vazquez-Tello, Abdullah Mohammed Alamri, Rabih Halwani, Abdullah Alangari, Abdurrahman Al-Frayh, Qutayba Hamid, Saleh Al-Muhsen, Arwa Ishaq Al-Khayyat, Mohammed Al-Anazi, Arjumand Warsy, Alejandro Vazquez-Tello, Abdullah Mohammed Alamri, Rabih Halwani, Abdullah Alangari, Abdurrahman Al-Frayh, Qutayba Hamid, Saleh Al-Muhsen

Abstract

Background and objectives: Genetic association studies have demonstrated that over 100 variants in target genes (including ADAM33) are associated with airway remodeling and hyper-responsiveness in different ethnic groups; however, this has never been evaluated in Arabic populations. The objective of this study was to determine whether ADAM33 polymorphisms that are associated with asthma in a population of asthmatic children from Saudi Arabia.

Design and setting: A cross-sectional pilot study comparing the polymorphisms of normal subjects and asthmatic patients from Saudi Arabia over a period of 1 year.

Patients and methods: One hundred and seven Saudi asthmatic children and 87 healthy Saudi children of 3-12 years old were assessed for allelic association of ADAM33 T1 (rs2280091), T2 (rs2280090), ST+4 (rs44707) and S1 (rs3918396) SNPs to asthma. Genotyping was done by real-time PCR, multiplex ARMS and PCR-RFLP.

Results: T1 and T2 SNP genotype frequencies in asthmatic children were significantly different compared to controls (P < .05), indicating allelic association with asthma. The T1 A/G and G/G and the T2 A/G and A/A genotypes (P=.0013 and P=.008, respectively) but not S1 and ST+4, increased the risk of asthma when using the best fit dominant model. Strong linkage disequilibrium between T1 (rs2280091) and T2 (rs2280090) was observed (r2=0.83; D'=0.95; P < .001). The haplotype G-A-A-C was significantly more frequent in asthmatics, thus supporting the association of T1 G-allele and T2 A-allele with increased predisposition to asthma (P=.007).

Conclusions: T1 A/G and T2 G/A ADAM33 polymorphisms, but not S1 or ST+4, were significantly associated with asthma development in Saudi children, like those reported for white and Hispanic populations in the United States.

Figures

Figure 1
Figure 1
Genomic structure of ADAM33 and the location of the 4 SNPs genotype. The 22 exons are shown as boxes and designated by the letters A through V. The SNPs and allele frequencies in Saudi compared to other populations are shown in the table.

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