Genetic Polymorphisms of the beta2-Adrenergic Receptor in the Severity of Bronchial Asthma

Shim, Jae Jeong; Kim, Jei Hyung; Lee, Seung Yung; Kwan, Young Hwan; Lee, So Ra; Lee, Sang Youb; Kang, Se Yung; Kang, Yong Koo; Cho, Jae Yun; In, Kwang Ho; Won, Nam Hee; Yoo, Se Hwa; Kang, Kyung Ho

Abstract

BACKGROUND: Genetic and environmental factors are known to affect the incidence and severity of asthma. Stimulation of beta2-Adrenergic Receptor (beta 2AR) results in smooth muscle relaxation, leading to decrease in resistance of airflow. The gene encoding the beta 2AR has recently been seguenced. The beta 2AR genotype at the polymorphic lociof codons 16, 27, 34, and 164 was known to cause changes in the amino acids. The relationships between the structure of the beta 2AR and its functions are being elucidated. PURPOSE: The gene encoding the beta 2AR was carried out to assess the frequency of polymorphisms in bronchial asthma, to determine wheather these polymorphisms have any relation to the severity, or nocturnal symptoms in bronchial asthma. METHOD: The subjects studied were 103 patients with bronchial asthma, which consisted of 30 mild episodic, 32 mild persistent, 17 moderate, and 24 severe asthma patients. The polymorphisms of the beta 2AR gene were detected by mutated allele specific amplification (MASA) method at the codons 16, 27, 34, and 164.
RESULTS
The most frequent polymorphism was arginine 16 to glycine. The other two polymorphisms, valine 34 to methionine and glutamine 27 to glutamic acid occured in 11 and 6 patients respectively. The polymorphism of threonine 164 to isoleucine was not found in our enrolled patients. The homozygous polymorphism of beta 2AR gene was found in only arginine 16 to glycine (12.6%). The heterozygous polymorphisms of beta 2AR gene were in arginine 16 to glycine, valine 34 to methionine, and glutamine 27 to glutamic acid, as 65.1%, 10.7%, and 5.8% respectively in asthma patients. The presence of agrginine 16 to glycine heterozygous or/and homozygous polymorphism was associated in severe asthma (p=0.015), but there was no association between the other three polymorphisms and the severity of asthma. The frequency of the 182AR gene polymorphisms was no relation in nocturnal asthma as compared with non-nocturnal asthma.
CONCLUSION
The arginine 16 to glycine polymorphism of the beta 2AR gene is the most frequently found in asthma patients and association with severe asthma. But there was no association between the polymorphism of the beta 2AR gene and nocturnal asthma.