Association between Major Single Nucleotide Polymorphism and Haplotype of the ADRB2 Gene and Korean Children with Asthma / 소아알레르기및호흡기학회지

ABSTRACT

PURPOSE: Development of asthma involves the interaction between genetic factors and environmental stimuli. This study aims to investigate whether major single nucleotide polymorphism (SNP)s and their haplotypes of the ADRB2 (beta2-adrenoceptor) gene are associated with children with asthma in Korea. METHODS: Children with asthma aging 5 to 15 years old were recruited as the patient group, and children without respiratory diseases or asthma of the same age were recruited as the control group. Blood samples of 5 mL were collected and DNA was extracted by standard methods. Genotyping was done for 6 SNPs known to have a frequency of more than 4%, including 1309A>G, 1342C>G, 1515G>A, 1786C>A, 2316G>C, 2502G>A. RESULTS: Overall, 438 subjects (214 patients and 224 controls) were included in this study. Minor allele homozygote frequency of 6 SNP were 22%, 1.8%, 11%, 12.3%, 21.2% and 13.0%, respectively. Differences between both groups of individual SNP frequencies were not statistically significant, although the difference of the frequency of the second SNP (1342C>G) has borderline significance (P=0.06). Overall distributions of haplotypes were not significantly different between both groups. However, analysis of specific SNPs among haplotypes revealed that haplotypes including the 2nd SNP were significantly associated with asthma (odds ratio, 1.7; 95% confidence interval, 1.1 to 2.6). Combinations of haplotypes excluding the 2nd SNP did not show significant difference between both groups. CONCLUSION: This study suggests that the ADRB2 gene polymorphism is associated with susceptibility to childhood asthma and that analysis of haplotypes rather than SNPs is more reliable in this association.