The Serotonin Transporter Polymorphism rs25531 Is Associated with Irritable Bowel Syndrome

被引:53
作者
Kohen, Ruth [1 ,2 ]
Jarrett, Monica E. [3 ]
Cain, Kevin C. [4 ]
Jun, Sang-Eun [3 ]
Navaja, Grace P. [1 ]
Symonds, Sarah [1 ]
Heitkemper, Margaret M. [3 ]
机构
[1] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA
[2] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA
[3] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA
[4] Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98195 USA
关键词
Irritable bowel syndrome; Functional gastrointestinal disorders; Serotonin transporter; Serotonin; Genetic polymorphism; OBSESSIVE-COMPULSIVE DISORDER; FUNCTIONAL POLYMORPHISM; GENE POLYMORPHISM; PREDOMINANT; EXPRESSION; PROTEIN; CONSTIPATION; GENOTYPES; 5-HTTLPR; COCAINE;
D O I
10.1007/s10620-008-0666-3
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Irritable bowel syndrome is a frequent gastrointestinal disorder of unknown etiology. The serotonin transporter regulates the intensity and duration of serotonin signaling in the gut and is, therefore, an attractive candidate gene for irritable bowel syndrome. Previous studies investigating the 5-HTTLPR and Stin2 VNTR polymorphisms of the serotonin transporter have proved inconclusive. In this exploratory study we therefore expanded the search for a possible association of the serotonin transporter with irritable bowel syndrome to include not only the 5-HTTLPR and Stin2 VNTR length polymorphisms, but also the functional single nucleotide polymorphism rs25531. We genotyped 186 patients with irritable bowel syndrome and 50 healthy control subjects raging in age from 18 to 70 years. Carriers of the rare G allele of rs25531 had approximately threefold increased odds of irritable bowel syndrome compared with healthy controls (OR 3.3, 95% CI 1.1-9.6). Our findings suggest that further investigation of the possible role of the serotonin transporter in the etiology of IBS is warranted.
引用
收藏
页码:2663 / 2670
页数:8
相关论文
共 41 条
[1]   Irritable bowel syndrome - Recent and novel therapeutic approaches [J].
Andresen, Viola ;
Camilleri, Michael .
DRUGS, 2006, 66 (08) :1073-1088
[2]   Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndrome [J].
Atkinson, W ;
Lockhart, S ;
Whorwell, PJ ;
Keevil, B ;
Houghton, LA .
GASTROENTEROLOGY, 2006, 130 (01) :34-43
[3]   Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron [J].
Bellini, M ;
Rappelli, L ;
Blandizzi, C ;
Costa, F ;
Stasi, C ;
Colucci, R ;
Giannaccini, G ;
Marazziti, D ;
Betti, L ;
Baroni, S ;
Mumolo, MG ;
Marchi, S ;
Del Tacca, M .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2003, 98 (12) :2705-2711
[4]   Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: Abnormal intestinal motility and the expression of cation transporters [J].
Chen, JJ ;
Li, ZS ;
Pan, H ;
Murphy, DL ;
Tamir, H ;
Koepsell, H ;
Gershon, MD .
JOURNAL OF NEUROSCIENCE, 2001, 21 (16) :6348-6361
[5]   Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome [J].
Coates, MD ;
Mahoney, CR ;
Linden, DR ;
Sampson, JE ;
Chen, J ;
Blaszyk, H ;
Crowell, MD ;
Sharkey, KA ;
Gershon, MD ;
Mawe, GM ;
Moses, PL .
GASTROENTEROLOGY, 2004, 126 (07) :1657-1664
[6]   Irritable bowel syndrome: Epidemiology, natural history, health care seeking and emerging risk factors [J].
Cremonini, F ;
Talley, NJ .
GASTROENTEROLOGY CLINICS OF NORTH AMERICA, 2005, 34 (02) :189-+
[7]   Role of serotonin in the pathophysiology of the irritable bowel syndrome [J].
Crowell, MD .
BRITISH JOURNAL OF PHARMACOLOGY, 2004, 141 (08) :1285-1293
[8]  
Drossman DA, 2002, GASTROENTEROLOGY, V123, P2108, DOI 10.1053/gast.2002.37095
[9]  
DROSSMAN DA, 2000, ROME, V2
[10]   The AP-2 family of transcription factors [J].
Eckert, Dawid ;
Buhl, Sandra ;
Weber, Susanne ;
Jaeger, Richard ;
Schorle, Hubert .
GENOME BIOLOGY, 2005, 6 (13)