β2肾上腺素能受体5'单倍型影响启动子活性。

Beta 2 adrenergic receptor 5' haplotypes influence promoter activity.

Johnatty Sharon E, Abdellatif Maha, Shimmin Lawrence, Clark Richard B, Boerwinkle Eric

Human Genetics Center, University of Texas School of Public Health, 1200 Herman Pressley RAS E477, Houston, TX 77030, U.S.A.

Br J Pharmacol. 2002 Dec;137(8):1213-6. doi: 10.1038/sj.bjp.0704935.

Transcriptional control of the human beta(2) adrenergic receptor gene (ADRB2) predominantly resides within a 549 base pair region immediately 5' to the start of translation. Within this region, four naturally occurring polymorphisms, -468 C-->G, -367 T-->C, -47 T-->C, and -20 T-->C, have been identified. 2. To determine the individual site and haplotype effects of these polymorphisms, we generated 16 luciferase-based mutant constructs which were transiently transfected into HEK293 cells, and measured ADRB2 promoter-driven luciferase activity. 3. Two of the 16 mutant constructs, GCCT (-468G, -367C, -47C, -20T) and CTCT, showed a highly significant 3 fold decrease in luciferase induction relative to the reference CTTT. These haplotype effects could not be accounted for by the separate and additive effects of each site. 4. These findings indicate that promoter polymorphisms interact to significantly alter beta(2) adrenergic receptor expression, and should be examined further for their association with disease-related phenotypes.

人类β₂肾上腺素能受体基因（ADRB2）的转录调控主要位于翻译起始位点上游紧邻的一个549碱基对区域内。在该区域，已鉴定出四种天然存在的多态性，即 -468 C→G、-367 T→C、-47 T→C和 -20 T→C。2. 为了确定这些多态性的单个位点和单倍型效应，我们构建了16个基于荧光素酶的突变体构建体，将其瞬时转染到HEK293细胞中，并测量ADRB2启动子驱动的荧光素酶活性。3. 16个突变体构建体中的两个，GCCT（-468G、-367C、-47C、-20T）和CTCT，相对于参考CTTT，荧光素酶诱导活性显著降低了3倍。这些单倍型效应不能用每个位点的单独和累加效应来解释。4. 这些发现表明，启动子多态性相互作用可显著改变β₂肾上腺素能受体的表达，应进一步研究它们与疾病相关表型的关联。

Beta 2 adrenergic receptor 5' haplotypes influence promoter activity.