Beta 2 adrenergic receptor gene restriction fragment length polymorphism and bronchial asthma.

Abstract

Results -A two allele polymorphism (2-3 kb and 2-1 kb) of the P2ADR gene was detected in the Japanese population. Family members without allele 2-3 kb (homozygote of allele 2l pkb) had lower airways responses to inhaled salbutamol than those with allele 2-3 kb. The incidence of asthma was higher in those without allele 2-3 kb than in those with allele 2 3 kb. The P2ADR gene RFLP had no relation to airways responses to methacholine and atopic status. cAMP responses in peripheral mononuclear cells of the subjects without allele 2-3kb tended to be lower than those ofthe subjects with allele 2*3 kb. This locus is close to the locus called "5q cluster" in which the genes for IL-3, IL-4, IL-5, and granulocyte-macrophage colony stimulating factor (GM-CSF) are located. In addition, DNA polymorphism of the P2ADR with Ban-I digestion has been examined and a two allele polymorphism has been reported in 20 unrelated white people in North America.'2 ConclusionsWe have therefore examined the 12ADR gene restriction fragment length polymorphism (RFLP) in a Japanese population of 58 family members of four atopic asthmatic patients and investigated the relation to atopic state, nonspecific bronchial hyperresponsiveness to methacholine, airways responses to a 12 agonist, and the incidence of physician diagnosed asthma. Methods SUBJECT SELECTIONA total of 58 subjects, family members of four patients with bronchial asthma, were examined. They comprised three generations with 17, 12, 13, and 16 subjects from each family. The

Beta-2 adrenergic receptor variants are associated with subcutaneous fat accumulation in response to long-term overfeeding

“…Some earlier studies have suggested that, although not causing a change in the sequence of the receptor molecule, the mutation detected with BanI could be related to the ADRB2 function. 17 The mutation is located at nucleic acid residue 523 14 and is in linkage disequilibrium with codon 16 15 and 27 polymorphisms. 15,18 Therefore, the effects of the ADRB2 BanI polymorphism identified here could be mediated by its linkage disequilibrium with the codon 27 polymorphism, as the codon 16 variant was not associated with the response to overfeeding in these young men.…”

Complex promoter and coding region β 2 -adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness

“…In the former, eight SNPs were identified as shown in Table 1. Within the ORF, sequence was determined from the start codon through nucleotide 523, which is a synonymous SNP that has been reported to be associated with the response to albuterol (14). As shown, this region also contains all of the known nonsynonymous SNPs that alter the encoded residues at amino acid positions 16, 27, and 164 of the protein (1).…”

“…Haplotype 4 expression was less than haplotype 2 at P Ͻ 0.005. and Ϫ468 each flank an NF-1 consensus sequence; and the SNP at Ϫ367 is within a CP2 consensus sequence. Of note, the synonymous SNP at position 523 that has been associated with altered responsiveness to albuterol in Japanese families (14) was invariant between haplotypes 2 and 4. However, this SNP along with several others distinguishes one common haplotype (haplotype 6) from the others.…”

“…Given the in vitro findings with the polymorphic ␤ 2 AR, we and others have considered that these SNPs may act as disease modifiers in asthma or may be the basis for the variability in the response to ␤ agonists (11). Indeed, some studies have shown that an individual ␤ 2 AR SNP correlates with the bronchodilatory response to ␤ agonists (12)(13)(14) or the extent of tachyphylaxis to repeated use of these agents (15,16). Other studies, although, have failed to show any such correlations (17) or have shown discordant results (15,16).…”

Pharmacogenetic Differences in Response to Albuterol between Puerto Ricans and Mexicans with Asthma

“…Polymorphisms in the β 2 AR gene have been inconsistently associated with varying degrees of bronchodilatory response to β-agonists [7][8][9][10][11][12] and with tachyphylaxis. 13,14 In one study, specific haplotypes, as opposed to individual single nucleotide polymorphisms (SNPs), were significantly associated with drug responsiveness.…”