Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastrointestinal disorders
Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastrointestinal disorders
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DOI：
10.1152/ajpgi.90650.2008
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发表时间：
2009-03-01
影响因子：
4.5
通讯作者：
Boles, Richard G.
中科院分区：
文献类型：
--
作者：
Camilleri, Michael;Carlson, Paula;Boles, Richard G.
首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容线粒体DNA与胃肠运动和感觉功能在健康和功能性胃肠疾病中的作用。Am J Physiol胃肠病肝生理学296：G510-G516,2009。2009年1月15日首次出版；doi：10.1152/ajpgi.90650.2008。-参与胃肠道(GI)功能的神经、肌肉和炎症细胞具有高能量需求，并受到线粒体疾病的影响。肠易激综合征(IBS)的家族聚集性通常涉及母亲和她们的孩子。由于线粒体DNA(MtDNA)是母系遗传的，mtDNA单核苷酸多态(SNPs)可增加IBS的发病风险。线粒体DNA SNPs，16519C>；T和3010G>；A与偏头痛和儿童周期性呕吐综合征有关。我们的假设是，这些mtDNA SNPs与功能性胃肠道疾病(FGID)和胃肠道功能有关。首先对699名患者或对照组进行了mt基因组7028C多态(定义单倍组H)的检测，并对那些携带7028C的患者进行了16519和3010点的进一步基因分型。表型基于症状(经过验证的问卷和标准)和胃肠道生理学，使用经过验证的运动和感觉研究。便秘为主的IBS和便秘和腹泻交替的IBS在具有7028C mtDNA多态的个体中的患病率低于7028T的个体。相反，与7028T相比，7028C与更高的最大耐受量(较低的饱合度)相关。在7028C携带者中，非特异性腹痛(慢性腹痛或消化不良)与3010A和3010G显著相关(优势比3.3，P=0.02)，胃排空减慢与3010G显著相关。检测的mtDNA基因类型与胃容量、小肠或结肠运输、直肠顺应性以及运动或感觉功能之间没有显著的相关性。因此，mtDNA的变异可能与饱腹感、胃排空和可能的疼痛有关；进一步研究mtDNA在食欲调节和更多FGIDs患者中的作用是有必要的。
Camilleri M, Carlson P, Zinsmeister AR, McKinzie S, Busciglio I, Burton D, Zaki EA, Boles RG. Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastrointestinal disorders. Am J Physiol Gastrointest Liver Physiol 296: G510-G516, 2009. First published January 15, 2009; doi:10.1152/ajpgi.90650.2008.-Nerve, muscle, and inflammatory cells involved in gastrointestinal (GI) function have high-energy requirements and are affected in mitochondrial disorders. Familial aggregation of irritable bowel syndrome (IBS) frequently involves mothers and their children. Since mitochondrial DNA (mtDNA) is maternally inherited, mtDNA single nucleotide polymorphisms (SNPs) could confer risk to the development of IBS. The mtDNA SNPs, 16519C>T and 3010G>A, are associated with migraine and childhood cyclic vomiting syndrome. Our hypothesis is that these mtDNA SNPs are associated with functional GI disorders (FGIDs) and GI functions. The mt genome was first tested for the 7028C polymorphism (defining haplogroup H) in 699 patients or controls, and those with 7028C were further genotyped at 16519 and 3010. Phenotypes were based on symptoms (validated questionnaires and criteria) and GI physiology using validated motor and sensory studies. Constipation-predominant IBS and alternating constipation and diarrhea IBS are less prevalent in individuals with the 7028C mtDNA polymorphism than in individuals with 7028T. Conversely, 7028C is associated with higher maximum tolerated volume (lower satiation) compared with 7028T. Among those with 7028C, nonspecific abdominal pain (chronic abdominal pain or dyspepsia) was significantly associated with 3010A compared with 3010G (odds ratio 3.3, P = 0.02), and slower gastric emptying was statistically associated with 3010G. There were no significant associations of mtDNA genotypes tested and stomach volumes, small bowel or colonic transit, rectal compliance, and motor or sensory functions. Thus variation in mtDNA may be associated with satiation, gastric emptying, and possibly pain; further studies of mtDNA in appetite regulation and larger numbers of patients with FGIDs are warranted.