Kohen Ruth, Tracy Julia H, Haugen Eric, Cain Kevin C, Jarrett Monica E, Heitkemper Margaret M
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Biol Res Nurs. 2016 Jul;18(4):394-400. doi: 10.1177/1099800416633296. Epub 2016 Feb 24.
Alterations in serotonin signaling are suspected in the pathophysiology of irritable bowel syndrome (IBS). By modulating the extracellular reuptake of serotonin, the serotonin transporter (SERT) acts as a key regulator of the bioavailability of serotonin. This study is the first to investigate the impact of rare SERT variants (i.e., those with a minor allele frequency of < 1%) on the risk for IBS, gastrointestinal (GI) symptom level, response to cognitive-behavioral treatment, and psychiatric comorbidity. We sequenced a 0.19 megabase chromosomal stretch containing the SERT gene and surrounding regions in a community sample of 304 IBS patients and 83 controls. We found no significant associations between rare variants in and around the SERT gene and IBS risk, GI symptom profile, or response to treatment. We found preliminary evidence, however, that IBS subjects with a history of either depression or anxiety were significantly more likely to carry multiple rare likely functional variant alleles than IBS patients without psychiatric comorbidity.
血清素信号传导的改变被怀疑与肠易激综合征（IBS）的病理生理学有关。通过调节血清素的细胞外再摄取，血清素转运体（SERT）作为血清素生物利用度的关键调节因子发挥作用。本研究首次调查罕见SERT变异（即次要等位基因频率<1%的变异）对IBS风险、胃肠道（GI）症状水平、认知行为治疗反应和精神共病的影响。我们对304例IBS患者和83例对照的社区样本中包含SERT基因及周边区域的0.19兆碱基染色体片段进行了测序。我们发现SERT基因及其周围的罕见变异与IBS风险、GI症状特征或治疗反应之间无显著关联。然而，我们发现初步证据表明，有抑郁或焦虑病史的IBS患者比无精神共病的IBS患者携带多个罕见的可能具有功能的变异等位基因的可能性显著更高。
