title: Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastrointestinal disorders.
abstract: Nerve, muscle, and inflammatory cells involved in gastrointestinal (GI) function have high-energy requirements and are affected in mitochondrial disorders. Familial aggregation of irritable bowel syndrome (IBS) frequently involves mothers and their children. Since mitochondrial DNA (mtDNA) is maternally inherited, mtDNA single nucleotide polymorphisms (SNPs) could confer risk to the development of IBS. The mtDNA SNPs, 16519C>T and 3010G>A, are associated with migraine and childhood cyclic vomiting syndrome. Our hypothesis is that these mtDNA SNPs are associated with functional GI disorders (FGIDs) and GI functions. The mt genome was first tested for the 7028C polymorphism (defining haplogroup H) in 699 patients or controls, and those with 7028C were further genotyped at 16519 and 3010. Phenotypes were based on symptoms (validated questionnaires and criteria) and GI physiology using validated motor and sensory studies. Constipation-predominant IBS and alternating constipation and diarrhea IBS are less prevalent in individuals with the 7028C mtDNA polymorphism than in individuals with 7028T. Conversely, 7028C is associated with higher maximum tolerated volume (lower satiation) compared with 7028T. Among those with 7028C, nonspecific abdominal pain (chronic abdominal pain or dyspepsia) was significantly associated with 3010A compared with 3010G (odds ratio 3.3, P=0.02), and slower gastric emptying was statistically associated with 3010G. There were no significant associations of mtDNA genotypes tested and stomach volumes, small bowel or colonic transit, rectal compliance, and motor or sensory functions. Thus variation in mtDNA may be associated with satiation, gastric emptying, and possibly pain; further studies of mtDNA in appetite regulation and larger numbers of patients with FGIDs are warranted.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Charlton 8-110, 200 First St. S.W., Rochester, MN 55905, USA. camilleri.michael@mayo.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Paula
authors.initials: P
authors.lastname: Carlson
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: Sanna
authors.initials: S
authors.lastname: McKinzie
authors.forename: Irene
authors.initials: I
authors.lastname: Busciglio
authors.forename: Duane
authors.initials: D
authors.lastname: Burton
authors.forename: Essam A
authors.initials: EA
authors.lastname: Zaki
authors.forename: Richard G
authors.initials: RG
authors.lastname: Boles
mesh_terms: D000328:Adult; D003248:Constipation / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D004415:Dyspepsia / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D017615:Enteric Nervous System / Q000502:physiology*; D005767:Gastrointestinal Diseases / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D011984:Sensory Receptor Cells / Q000502:physiology
chemical_list: D004272:DNA, Mitochondrial