title: Mitochondrial ATP 6 and 8 polymorphisms in irritable bowel syndrome with diarrhea.
abstract: OBJECTIVE
  To investigate mitochondrial ATP 6 and 8 polymorphisms in the colon and ileum of patients with irritable bowel syndrome with diarrhea (IBS-D).
  
  
  METHODS
  Twenty-eight patients fulfilling the Rome III criteria for IBS-D and 28 healthy subjects were investigated. All study participants underwent screening colonoscopy and mucosal biopsies were obtained from the colon and/or terminal ileum. Genomic DNA was extracted from specimens based on standard protocols. Mitochondrial ATP (MT-ATP) 6 and 8 genes in specimens were polymerase chain reaction amplified and sequenced. Sequencing data were analyzed via Variant Reporter™ Software and compared with the reference sequence from Genbank (accession No. NC_012920) to indicate possible polymorphisms. The protocol was registered at www.clinicaltrials.gov as NCT01028898.
  
  
  RESULTS
  Twenty-five polymorphic sites of MT-ATP 6 and 8 genes were detected and 12 of them were missense mutations. A median of two polymorphic sites in MT-ATP genes was found in colon specimens of controls while a median of three polymorphic sites was noted in patients with IBS-D (Mann-Whitney test, P = 0.012). The variants of the colon and ileum specimens from the same subjects were identical in all but one case. Symptom duration in IBS was not found to be a significant factor associated with the mtDNA polymorphism (Spearman correlation, P = 0.592). The mitochondrial DNA change at 8860 was present in all cases of both groups. The frequency of the 8701 polymorphism was found to be the second most frequent; however, no statistical difference was noted between the groups (χ(2) test, P = 0.584).
  
  
  CONCLUSIONS
  Patients with IBS-D have a higher incidence of MT-ATP 6 and 8 polymorphisms than healthy subjects, implying that the mtDNA polymorphism may play a role in IBS-D.
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Ming-Zhou
authors.initials: MZ
authors.lastname: Guo
authors.forename: Jian-De
authors.initials: JD
authors.lastname: Chen
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Yang
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Peng
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Wang
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Zhang
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D003106:Colon / Q000473:pathology; D003113:Colonoscopy; D015897:Comorbidity; D003967:Diarrhea / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D006801:Humans; D007082:Ileum / Q000473:pathology; D015994:Incidence; D043183:Irritable Bowel Syndrome / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: C501005:MT-ATP6 protein, human; D025261:Mitochondrial Proton-Translocating ATPases
keywords: Diarrhea; Irritable bowel syndrome; Mitochondrial ATP 6 gene; Mitochondrial ATP 8 gene; Polymorphism