Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA.
Aliment Pharmacol Ther. 2013 Aug;38(3):313-23. doi: 10.1111/apt.12378. Epub 2013 Jun 20.
The beta-2 adrenergic receptor (ADRB2) is an important target for epinephrine, a neurotransmitter in pain signalling. ADRB2 haplotypes affect receptor expression and ligand response, and have been linked to painful non-GI disorders.
To assess whether ADRB2 polymorphisms (rs1042713, rs1042714) are risk alleles for functional GI (FGID) and extraintestinal functional (EIFD) diagnoses, and whether ADRB2 predicts GI symptoms and health-related quality of life (HRQOL).
Of 398 subjects (49.6 ± 2.9 years, 68.0% female), 170 (42.5%) met Rome III criteria for ≥1 FGID [IBS (n = 139, 34.9%); functional dyspepsia (FD, n = 136, 34.1%), functional chest pain (FCP, n = 25, 6.2%)], while 228 were healthy controls. FGID subjects reported on bowel symptom severity and burden (10-cm VAS), frequency (days/last 2 weeks), EIFD, psychiatric diagnoses and HRQOL (SF 36). Multivariable models determined the contribution of ADRB2 polymorphisms to HRQOL, and mediational analyses assessed functional diagnoses as potential intermediates.
rs1042714 minor G alleles were associated with FGID diagnoses (OR 1.8; 95% CI 1.2-2.7; P = 0.009), particularly FD (OR 2.1, 95% CI 1.3-3.3), with trends towards IBS (P = 0.19) and FCP (P = 0.06) diagnoses. Within IBS, G allele carriers had more severe bowel symptoms (P = 0.025), and symptomatic days (P = 0.009). G allele carriers had greater numbers of EIFD (1.0 ± 0.1 vs. 0.4 ± 0.07, P < 0.001) and poorer HRQOL. The effect of ADRB2 on HRQOL was partially mediated by FGID, EIFD and psychiatric diagnoses.
ADRB2 minor alleles at rs1042714 predict FGID and EIFD, and may influence bowel symptom severity and HRQOL. These findings provide indirect evidence of sympathetic nervous system role in FGID pathophysiology.
β-2 肾上腺素能受体（ADRB2）是神经递质疼痛信号传导中的去甲肾上腺素的重要靶点。ADRB2 单倍型影响受体表达和配体反应，并与非胃肠道疼痛障碍有关。
评估 ADRB2 多态性（rs1042713、rs1042714）是否为功能性胃肠道（FGID）和肠外功能性（EIFD）诊断的风险等位基因，以及 ADRB2 是否可预测胃肠道症状和健康相关生活质量（HRQOL）。
在 398 名受试者中（49.6±2.9 岁，68.0%为女性），170 名（42.5%）符合罗马 III 标准，存在≥1 种 FGID[肠易激综合征（IBS，n=139，34.9%）；功能性消化不良（FD，n=136，34.1%），功能性胸痛（FCP，n=25，6.2%）]，而 228 名是健康对照组。FGID 患者报告肠道症状严重程度和负担（10cm VAS）、频率（每天/过去 2 周）、EIFD、精神科诊断和 HRQOL（SF-36）。多变量模型确定 ADRB2 多态性对 HRQOL 的贡献，中介分析评估功能性诊断是否为潜在的中介因素。
rs1042714 次要 G 等位基因与 FGID 诊断相关（OR 1.8；95%CI 1.2-2.7；P=0.009），尤其是 FD（OR 2.1，95%CI 1.3-3.3），与 IBS（P=0.19）和 FCP（P=0.06）诊断呈趋势相关。在 IBS 中，G 等位基因携带者的肠道症状更严重（P=0.025），症状天数更多（P=0.009）。G 等位基因携带者的 EIFD 更多（1.0±0.1 与 0.4±0.07，P<0.001），HRQOL 更差。ADRB2 对 HRQOL 的影响部分通过 FGID、EIFD 和精神科诊断来介导。
rs1042714 的 ADRB2 次要等位基因预测 FGID 和 EIFD，并可能影响肠道症状严重程度和 HRQOL。这些发现提供了交感神经系统在 FGID 病理生理学中作用的间接证据。
