4.2 Article

Association of Fatigue With TPH2 Genetic Polymorphisms in Women With Irritable Bowel Syndrome

期刊

BIOLOGICAL RESEARCH FOR NURSING
卷 21, 期 1, 页码 72-79

出版社

SAGE PUBLICATIONS INC
DOI: 10.1177/1099800418806055

关键词

fatigue; irritable bowel syndrome; genetic polymorphisms; tryptophan hydroxylase; serotonin reuptake transporter; catechol-O-methyltransferase

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资金

  1. U.S. National Institutes of Health, National Institute of Nursing Research [NR004142, P30 NR04001]
  2. National Cancer Institute (NCI) Biobehavioral Cancer Prevention and Control Training Program at the University of Washington, Department of Public Health [5T32CA092408-17]
  3. Fred Hutchinson Cancer Research Center, Seattle, WA

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Fatigue is the most common extraintestinal symptom in women with irritable bowel syndrome (IBS). Genetic polymorphisms of monoamines are associated with fatigue in many chronic diseases. In this pilot exploratory study, the primary aim was to determine whether genetic polymorphisms of tryptophan hydroxylase (TPH1/TPH2), serotonin reuptake transporter (SERT), or catechol-O-methyltransferase (COMT) are associated with fatigue in women with IBS. Additionally, analysis explored whether these genetic associations with fatigue would be present when controlling for abdominal pain, psychological distress, feeling stressed, and sleepiness during the day. Secondary analysis of two randomized controlled trial baseline data sets in Caucasian women with IBS (N = 185) was conducted. Participants kept a daily diary with one dimension (i.e., severity) for each of the 26 symptoms, including fatigue, for 28 days prior to randomization. DNA samples were tested for single-nucleotide polymorphisms (SNPs) of TPH1 (four SNPs)/TPH2 (one SNP), SERT (one SNP), and COMT (one SNP). Analysis of covariance was used to examine associations of percentage of diary days with moderate to very severe symptoms with genetic polymorphisms. Only one SNP, TPH2 rs4570625, was significantly associated with fatigue (p = .005). T-allele (low functional) carriers of TPH2 (i.e., G/T or T/T genotypes) reported a greater percentage of days with moderate to very severe fatigue than G/G homozygotes (p = .001). Reduced synthesis of tryptophan in the central nervous system may contribute to reports of fatigue in women with IBS. Understanding genetic risk factors for fatigue may elucidate preemptive strategies to reduce fatigue in individuals with IBS.

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