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

ABSTRACT

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. A cross-sectional pilot study comparing the polymorphisms of normal subjects and asthmatic patients from Saudi Arabia over a period of 1 year. 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. 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=0.0013 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]. 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 population in the United States