Duke University School of Medicine, Durham VA Medical Center, Durham, NC, USA.
Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA.
Aliment Pharmacol Ther. 2018 Jan;47(2):289-297. doi: 10.1111/apt.14414. Epub 2017 Nov 17.
Genetic polymorphisms in G-protein beta-3 subunit (GNβ3) and beta-2 adrenergic receptor (ADRB2) are associated with pain and gut hypersensitivity, which can overlap with gastroesophageal reflux disease (GERD).
To evaluate relationships between single nucleotide polymorphisms (SNPs) within GNβ3 and ADRB2 systems, and reflux symptom burden, GERD phenotypes from ambulatory reflux monitoring, and quality of life.
Symptomatic adults undergoing ambulatory reflux testing were recruited and phenotyped based on acid burden and symptom reflux association; major oesophageal motor disorders and prior foregut surgery were exclusions. A comparison asymptomatic control cohort was also identified. Subjects and controls completed questionnaires assessing symptom burden on visual analog scales, short-form health survey-36 (SF-36), and Beck Anxiety and Depression Inventories (BAI and BDI). Genotyping was performed from saliva samples; 6 SNPs selected from each of the two genes of interest were compared.
Saliva from 151 study subjects (55.3 ± 1.2 years, 63.6% F) and 60 control subjects (50.9 ± 2.2 years, 66.7%) had sufficient genetic material for genotyping. Study subjects had higher symptom burden, worse total and physical health, and higher anxiety scores compared to controls (P ≤ .002). Tested SNPs within ADRB2 were similar between study subjects and controls (P > .09). Study subjects with recessive alleles in 3 GNβ3 SNPs (Rs2301339, Rs5443, and Rs5446) had worse symptom severity (P = .011), worse mental health (P = .03), and higher depression scores (P = .005) despite no associations with GERD phenotypes or reflux metrics.
Genetic variation within GNβ3 predicts oesophageal symptom burden and affect, but not oesophageal acid burden or symptom association with reflux episodes.
G 蛋白β-3 亚基（GNβ3）和β-2 肾上腺素能受体（ADRB2）中的遗传多态性与疼痛和肠道高敏有关，这些与胃食管反流病（GERD）可能重叠。
评估 GNβ3 和 ADRB2 系统内的单核苷酸多态性（SNP）与反流症状负担、基于动态反流监测的 GERD 表型以及生活质量之间的关系。
招募有症状的成年人进行动态反流检测，并根据酸负荷和症状反流相关性进行表型分析；排除主要食管运动障碍和先前的前肠手术。还确定了无症状对照组。研究对象和对照组都完成了问卷调查，评估视觉模拟量表上的症状负担、健康调查简表 36 项（SF-36）以及贝克焦虑和抑郁量表（BAI 和 BDI）。从唾液样本中进行基因分型；比较了两个感兴趣基因中各选择的 6 个 SNP。
151 名研究对象（55.3 ± 1.2 岁，63.6%为女性）和 60 名对照者（50.9 ± 2.2 岁，66.7%为女性）的唾液有足够的遗传物质进行基因分型。与对照组相比，研究对象的症状负担更高，总健康和生理健康更差，焦虑评分更高（P ≤.002）。研究对象和对照组中 ADRB2 内的测试 SNP 相似（P >.09）。3 个 GNβ3 SNP（rs2301339、rs5443 和 rs5446）的隐性等位基因的研究对象的症状严重程度更差（P =.011），心理健康更差（P =.03），抑郁评分更高（P =.005），尽管与 GERD 表型或反流指标无关。
GNβ3 内的遗传变异预测食管症状负担和影响，但不预测食管酸负荷或反流事件与症状的相关性。
