Published online Jun 28, 2013. doi: 10.3748/wjg.v19.i24.3847
Revised: March 30, 2013
Accepted: April 9, 2013
Published online: June 28, 2013
Processing time: 142 Days and 6.4 Hours
AIM: 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 (χ2 test, P = 0.584).
CONCLUSION: 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.
Core tip: Mitochondrial DNA, the only source of extranuclear genome, was assessed by Camilleri’s group in a study of patients with functional gastrointestinal disorders in 2009 which was the first study exploring the possible role of mitochondrial DNA in irritable bowel syndrome (IBS). Up till now, few research efforts have focused on this topic and there is little knowledge about it. Present study revealed that mitochondrial ATP 6 and 8 genes were more frequently mutated in IBS with diarrhea than in healthy individuals. We believe this preliminary finding could help promote future research on mitochondrial DNA in IBS.