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

Jong Hun Kwak; Jeong Hee Kim; Dae Hyun Lim; Jun Mo Yang; Sin Young Park; Sung-Il Cho; Byong Kwan Son

doi:10.7581/pard.2012.22.4.354

Journal List > Pediatr Allergy Respir Dis > v.22(4) > 1033194

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Kwak, Kim, Lim, Yang, Park, Cho, and Son: Association between Major Single Nucleotide Polymorphism and Haplotype of the ADRB2 Gene and Korean Children with Asthma

Original Article

Pediatric Allergy and Respiratory Disease

Pediatric Allergy and Respiratory Disease 2012; 22(4): 354-363.

Published online: 31 December 2012

DOI: https://doi.org/10.7581/pard.2012.22.4.354

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

Jong Hun Kwak, MD, PhD¹, Jeong Hee Kim, MD, PhD^1,², Dae Hyun Lim, MD, PhD^1,², Jun Mo Yang, BS², Sin Young Park, MD³, Sung-Il Cho, MD, PhD⁴, Byong Kwan Son, MD, PhD^1,²

¹Department of Pediatrics, Inha University School of Medicine, Incheon, Korea.

²Environmental Health Center for Allergic Rhinitis, Inha University Hospital, Incheon, Korea.

³Department of Pediatrics, Jeju National University School of Medicine, Jeju, Korea.

⁴Department of Epidemiology, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Korea.

Corresponding author (sonbk@inha.ac.kr)

Received 10 September 2012 Revised 11 October 2012 Accepted 17 December 2012

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 (β2-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.

Keywords: Childhood asthma, Beta-2 adrenergic receptors, Single nucleotide polymorphism, Haplotype

Figures and Tables

Fig. 1

Pairwise linkage disequilibrium between single nucleotide polymorphism markers of the β2-adrenoceptor gene.

Table 1

PCR Primers for SNP Genotyping in The Loci of β2-Adrenoceptor Gene

PCR, polymerase chain reaction; SNP, single nucleotide polymorphism.

Table 2

General Characteristics of Subjects

Values are presented as number (%) or mean±standard deviation.

Calculated by chi-square test.

CI, confidence Interval.

^*Calculated by Student's t-test.

Table 3

Characteristics of Living Environment of Subjects

Values are presented as number (%).

CI, confidence Interval.

^*Calculated by chi-square test. ^†Calculated by Fisher's exacttest.

Table 4

The Distribution of β2-Adrenoceptor Genotypes

Values are presented as number (%).

OR, odds ratio; CI, confidence interval.

Table 5

The Frequencies of β2-Adrenoceptor Haplotypes

Values are presented as frequency (%).

Table 6

Frequencies of β2-Adrenoceptor Haplotypes and Asthma Risk from htSNPs Analysis

Values are presented as frequency (%).

OR, odds ratio; CI, confidence interval; htSNPs, haplotype-tagging SNP; SNP, single nucleotide polymorphism.

^*Likelihood ratio chi-square test.

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