| [Background and Aims] Functional bowel disorders include IBS, functional constipation and functional diarrhea, among which IBS is the most prevalent one. However the pathophysiology of it remains unclear. Our group has explored this area aiming to reveal the underlying pathogenesis in IBS. Previous studies by our group found that there were higher or lower expressions of several enzymes functioning in mitochondria and metabolism of nutrients. Also decreased ATP level in the intestine of IBS was found. All these findings were pointing to the abnormality of cellular energy metabolism. As mitochondria is the plant which is the main source of the cellular energy, further experiments are needed to clarify the role of mitochondria in IBS. Previous reports showed the evidence of familial aggregation of IBS. What's more, mothers as well as children seemed more involved in the family. As is known, mtDNA is characteristics of maternal inheritance. Furthermore, Camilleri's group explored the role of mtDNA haplogroup and polymorphisms in FGIDs and revealed haplogroup H,6519C＞T and 3010G>A, located in the D-loop and the 16S rRNA gene of mitochondrial DNA may be associated with gastrointestinal motor and sensory functions in IBS and other functional gastrointestinal disorders. The human mitochondrial genome encodes 13 genes for ATP subunits 6 and 8, and other polypeptides of respiratory complexes crucial for ATP production in mitochondria. The process of ATP synthesis depends on ATPase, of which subunits 6 and 8 are mtDNA-encoded. Hence we hypothesized that MT-ATP 6 and 8 may be involved in functional bowel disorders. The aim of this study was to investigate polymorphisms of mitochondrial ATP genes and the expression of mtDNA-encoded ATP subunits in patients with functional bowel disorders. [Material and Methods] In our study,48 cases were involved, among which there were 22 IBS patients with diarrhea,14 healthy subjects and 12 constipated patients who fulfilled the criteria for functional constipation or IBS with constipation. Biopsies were obtained from the colon and terminal ileum on colonoscopy. MT-ATP 6 and 8 genes in specimens were sequenced and mutations derived. Samples were also processed for detection of ATPase subunit 6 of human origin by Western blotting.[Results] 1. There is significant difference regarding gender between constipation group and controls but not between D-IBS and controls. No significant difference of age was found among these three groups.2. We detected 18 point mutations of MT-ATP 6 and 8 in the IBS group and 9 mutations in controls. Six mutations were shared between groups.52.4% were missense. Compared with controls, IBS patients had significantly more mutations of MT-ATP 6 and 8 genes. The mutations of the colon and ileum specimens from the same subjects were identical in all but one case. IBS duration was not a significant factor contributing to mtDNA mutations. The expressions of ATPase subunit 6 in D-IBS group were higher than those in controls.3. Compared with controls, each constipated patient demonstrated similar amount of mutations of MT-ATP 6 and 8 genes but the expressions of ATPase subunit 6 decreased.[Conclusions] IBS with diarrhea has a higher incidence of MT-ATP 6 and 8 mutations than healthy subjects but constipated patients don't. The expressions of ATPase subunit 6 in D-IBS group were higher but it was opposite in constipation group. Our findings imply that abnormal mtDNA mutations and ATPase expression play a potential role in IBS. Both the small and large intestine, harboring the same mtDNA mutation, indicates that a similar pathogenesis may exist in both locations.
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