Abstract
ADAM33 is the first reported asthma-susceptible gene identified by positional cloning. ADAM33 is located on chromosome 20p13 and codes for a protein important for cell fusion, cell adhesion, cell signaling, and proteolysis. Four polymorphic variants 11434C/A (rs44707), 6716 G/C (rs2787095), 7667 G/A (rs2485700), 400 A/G (rs2280091) were genotyped in 530 patients with physician-diagnosed asthma, aged 2-60 years (177 Russians, 110 Tatars, 68 Bashkirs and 175 mixed origins), and 366 nonasthmatic individuals (123 Russians, 91 Tatars, 51 Bashkirs and 101 mixed origins) from Volga-Ural region of Russia. A subgroup analysis of children and adults was conducted separately. Genotypes were determined by the PCR-RFLP method. Data were analyzed using the chi-square test with Haploview software. We found significant association of rs44707A allele (p=0.009, OR=1.56) with asthma susceptibility in Russian patients. Also the frequency of allele rs44707A was increased in adult asthmatics Russian ethnicity compared to controls (p=0.02, OR=1.73). Allele rs2280091G was found to be overrepresented in Bashkirs with asthma (p=0.04, OR=2.51). There were no significant differences in the allele frequencies in SNPs rs2787095, rs2485700 between asthma patients and control group. We constructed the haplotypes of cases and controls. Haplotype analysis showed that the haplotype CACA (rs44707, rs2787095, rs2485700, rs2280091) was more common in the control group than in the case group (p=1×10-4) and offered a protective effect against asthma in Russians. In summary, our results suggest an association between the ADAM33 gene polymorphisms and asthma in Russians and Bashkirs.
- © 2011 ERS