Association Analysis Of 3 SNPs In ADAM33 Gene With Asthma In A Chinese Han Population

Asthma is a recurrent and chronic inflammaroy pulmonary disorder caused by mix reaction of different inflammatory lymphocytes, such as eosinophile granulocyte, labrocyte and T cell. Asthma attacks repeatedly. The main symptoms include the obstruction of bronchial tubes, the increase of airway responsiveness, the airway inflammation and remodelling. Genetic epidemiology study reveals that asthma, as a polygenic disease, is induced by both hereditary factor and environmental factors. In recent years, researchers focus on study of susceptible genes of asthma for the investigation of mechanism. Nowadays hundreds of asthma susceptible genes have been reported within human genome, in which ADAM33 is a newly discovered one.In 2002, Van Eerdewegh first reported human ADAM33 gene as the susceptible gene of asthma. By genome-wide screening and positional cloning, Van Eerdewegh confirmed that ADAM33 gene on chromosome 20p13 was significantly linked to asthma (LOD=2.94) and bronchial hyperresponsiveness (LOD=3.93) in 460 Caucasian asthmatic families. Following research revealed that ADAM33 gene was associated with asthma and bronchial hyperresponsiveness (BHR) on different levels in ethnically different populations. Up till now, association of polymorphisms in ADAM33 gene with asthma has not been confirmed in Chinese population yet.In this study, 296 asthma patients and 270 healthy controls were recruited. DNA extracted from their peripheral blood were taken as research samples. SNPs were genotyped by PCR-RFLP (Restriction Fragment Length Polymorphism). All of them have been reported being associated with asthma or allergic disease with relative phenotype, but have not been investigated in Chinese population yet. At locus F+1, frequency of genotype G/G, G/A and A/A were 51.7%, 41.6%, 6.7% in asthma patients, while 48.5%, 46.7%, 4.8% in normal controls(P=0.361, x~2 test), frequencies of alleles C and T were 72.5% and 27.5% in asthma patients, while 71.9% and 28.1% in normal controls(P=0.818, x~2 test), no significant difference was observed. At S+1 site, frequency of genotype A/A, A/T, T/T were 28%, 53%, 19% in asthma patients, while 27.4%, 51.1%, 21.5% in normal controls(P=0.748, x~2 test), frequencies of alleles T and A were 45.4% and 54.6% in asthma patients, while 47% and 53% in normal controls (P=0.590, x~2 test), no significant difference was detected. At T1 site, frequency of genotype A/A, A/G, G/G were 84.5%, 15.2%, 0.3% in asthma patients, while 87.4%, 12.2%, 0.4% in normal controls(P=0.589, x~2 test), frequencies of allele A and allele G were 92.1% and 7.9% in asthma patients, while were 93.5% and 6.5% in normal controls(P=0.345, x~2 test), no significant difference was observed. Linkage diseqilibrium(LD) test showed that three loci were in week LD. None of genotype frequency, allele frequency or haplotype distribution of the three SNPs were statistically different between asthma patients and normal controls.The polymorphisms in this study showed no association with asthma in Chinese population. The role of polymorphisms in ADAM33 gene to pathogenesis of asthma will be clarified by studying large number samples and analyzing more SNPs.