beta2-Adrenergic receptor haplotypes in mild, moderate and fatal/near fatal asthma.
beta2-Adrenergic receptor haplotypes in mild, moderate and fatal/near fatal asthma.
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轻度、中度和致命/近乎致命哮喘中的β2-肾上腺素受体单倍型。
DOI：
10.1164/ajrccm.158.3.9801035
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Pare,PD
中科院分区：
文献类型：
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作者：
Weir,TD;Mallek,N;Sandford,AJ;Bai,TR;Awadh,N;Fitzgerald,JM;Cockcroft,D;James,A;Liggett,SB;Pare,PD
哮喘患者过量使用β2受体激动剂与死亡率和发病率增加有关。造成这些观察结果的机制尚不清楚。我们假设，β2-肾上腺素受体 (β2AR) 在氨基酸位置 16、27 和 164 处的多态性已知会在体外改变受体功能，可能会使哮喘患者易患致命/近乎致命的哮喘和/或改变哮喘的严重程度。在初步研究中，我们发现等位基因频率因种族背景而存在显着差异：白种人、黑人、亚洲人 Gly16 = 0.61、0.50、0.40 和 Gln27 = 0.57、0.73、0.80。 对白种人的 DNA 进行 β2AR 基因分型，这些人被分类为非哮喘/非特应性 (n = 84)、致命/近致命哮喘患者 (n = 81) 和轻度/中度哮喘患者 (n = 86)。没有发现多态性或单倍型与致命/近乎致命的哮喘相关。然而，在体外下调增强的 Gly16/Gln27 单倍型在中度哮喘患者中比在轻度哮喘患者中更为普遍（p = 0.003，比值比 = 3.1）。我们得出的结论是，β2AR 基因型不是致命性或近乎致命性哮喘的主要决定因素。此外，在哮喘β2AR多态性的临床研究中必须考虑种族之间的等位基因频率变异。
Excess β2-agonist use in asthmatics has been associated with increased mortality and morbidity. The mechanisms responsible for these observations are unknown. We hypothesized that polymorphisms of the β2-adrenergic receptor ( β2AR) at amino acid positions 16, 27, and 164, which are known to alter receptor functionsin vitro, may predispose asthmatics to fatal/near-fatal asthma and/or modify asthma severity. In preliminary studies we found significant differences in allele frequencies due to ethnic background: Caucasian, Black, Asian Gly16 = 0.61, 0.50, 0.40 and Gln27 = 0.57, 0.73, 0.80, respectively. β2AR genotyping was performed on DNA from Caucasians classified as nonasthmatic/nonatopic (n = 84), fatal/near-fatal asthmatics (n = 81) and mild/moderate asthmatics (n = 86). No polymorphism or haplotype was found to be associated with fatal/near-fatal asthma. However, the Gly16/Gln27 haplotype, which undergoes enhanced downregulationin vitro, was substantially more prevalent in moderate asthmatics than in mild asthmatics (p = 0.003, odds ratio = 3.1). We conclude that the β2AR genotype is not a major determinant of fatal or near-fatal asthma. Furthermore, allele frequency variation among ethnic groups must be considered in clinical studies of β2AR polymorphisms in asthma.