Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention
Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention
复制标题
DOI：
10.1016/j.neuroimage.2009.04.083
复制
发表时间：
2009-09-01
期刊：
影响因子：
5.7
通讯作者：
Aoki, M.
中科院分区：
文献类型：
--
作者：
Fukudo, S.;Kanazawa, M.;Aoki, M.
背景与目的：确定在脑-肠相互作用中起关键作用的基因是阐明肠易激综合征（IBS）病理生理学的关键一步。我们之前报道过5-羟色胺转运体基因连锁多态性区域（5-HTTLPR）与IBS患者的焦虑有关。携带5-HTTLPR s等位基因的人，在恐惧的面部识别过程中，杏仁核更加活跃。在这里，我们验证了我们的假设，即5-HTTLPR在人类中不同地激活与结肠直肠膨胀有关的大脑区域。方法：入选28例无器质性疾病的受试者。本研究经伦理委员会批准，所有受试者均给予书面知情同意。从外周血中提取了DNA。采用聚合酶链反应测定5-HTTLPR基因型。比较年龄、性别、诊断匹配的s/s基因型个体（n = 14）和I等位基因型个体（基因型为l/s、l/l、l/extra-1、n 14）。将一个气压袋插入结肠直肠，并按随机顺序间歇充气，无（0毫米汞柱）、轻度（20毫米汞柱）或强烈（40毫米汞柱）刺激。在充气袋处注射放射性H2 [O15-]生理盐水，然后进行正电子发射断层扫描。采用统计参数映射分析rCBF的变化。结果：s/s基因型个体结肠膨胀引起的rCBF从0 mm Hg增加到40 mm Hg显著高于I等位基因个体。s/s基因型个体的激活程度更高的大脑区域是左前扣带皮层和右海马旁回(p
Background and aims: Determining the gene that plays a key role in brain-gut interactions is a crucial step for clarifying the pathophysiology of irritable bowel syndrome (IBS). We previously reported that the 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is related to anxiety in Subjects with IBS. The amygdala is more activated during fearful face recognition in individuals with the s allele of 5-HTTLPR. Here, we tested our hypothesis that 5-HTTLPR differentially activates brain regions with colorectal distention in humans.Methods: We enrolled 28 Subjects without any organic disease. The Study was approved by the Ethics Committee and all subjects gave written informed consent. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Age, sex, diagnosis-matched individuals with the s/s genotype (n = 14) and individuals with the I allele (genotypes l/s, l/l, l/extra-1, n 14) were compared. A barostat bag was inserted to the colorectum and was intermittently inflated with no (0 mm Hg), mild (20 mm Hg), or intense (40 mm Hg) Stimulation on a random order. Radioactive H2 [O15-] saline was injected at bag inflation and then positron emission tomography was performed. Changes in rCBF were analyzed using statistical parametric mapping.Results: Individuals with the s/s genotype showed a significantly larger increase in rCBF by colorectal distention from 0 mm Hg to 40 mm Hg than individuals with the I allele. The significantly more activated brain regions in individuals with the s/s genotype were the left anterior cingulate cortex and right parahippocampal gyrus (p