Digestive Diseases and Sciences

, Volume 59, Issue 7, pp 1392–1397

Irritable Bowel Syndrome May Be Associated with Maternal Inheritance and Mitochondrial DNA Control Region Sequence Variants

  • Miranda A. L. van Tilburg
  • Essam A. Zaki
  • Thangam Venkatesan
  • Richard G. Boles
Original Article

DOI: 10.1007/s10620-014-3045-2

Cite this article as:
van Tilburg, M.A.L., Zaki, E.A., Venkatesan, T. et al. Dig Dis Sci (2014) 59: 1392. doi:10.1007/s10620-014-3045-2


Background and Aim

Mitochondrial dysfunction has been implicated in various functional disorders that are co-morbid to irritable bowel syndrome (IBS) such as migraine, depression and chronic fatigue syndrome. The aim of the current case–control pilot study was to determine if functional symptoms in IBS show a maternal inheritance bias, and if the degree of this maternal inheritance is related to mitochondrial DNA (mtDNA) polymorphisms.


Pedigrees were obtained from 308 adult IBS patients, 102 healthy controls, and 36 controls with inflammatory bowel disease (IBD), all from Caucasian heritage, to determine probable maternal inheritance. Two mtDNA polymorphisms (16519T and 3010A), which have previously been implicated in other functional disorders, were assayed in mtDNA haplogroup H IBS subjects and compared to genetic data from 344 published haplogroup H controls.


Probable maternal inheritance was found in 17.5 % IBS, 2 % healthy controls and 0 % IBD controls (p < .0001). No difference was found between IBS and control for 3010A, and a trend was found for 16519T (p = 0.05). IBS with maternal inheritance were significantly more likely to have the 16519T than controls (OR 5.8; 95 % CI 1.5–23.1) or IBS without maternal inheritance (OR 5.2; 95 % CI 1.2–22.6).


This small pilot study shows that a significant minority (1/6) of IBS patients have pedigrees suggestive of maternal inheritance. The mtDNA polymorphism 16519T, which has been previously implicated in other functional disorders, is also associated with IBS patients who display maternal inheritance. These findings suggest that mtDNA-related mitochondrial dysfunction may constitute a sub-group within IBS. Future replication studies in larger samples are needed.


Functional gastrointestinal disordersGeneticsCellular energy metabolismCo-morbidity



Inflammatory bowel disease


Irritable bowel syndrome


Mitochondrial DNA

Supplementary material

10620_2014_3045_MOESM1_ESM.pptx (55 kb)
Figure a: Example of a pedigree with maternal inheritance pattern (PPTX 54 kb)
10620_2014_3045_MOESM2_ESM.pptx (73 kb)
Figure b: Graph of maternal symptoms per relative by maternal inheritance ratios for irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and healthy controls (PPTX 73 kb)

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Miranda A. L. van Tilburg
    • 1
  • Essam A. Zaki
    • 2
    • 3
  • Thangam Venkatesan
    • 4
  • Richard G. Boles
    • 2
    • 3
  1. 1.Center for Functional GI and Motility DisordersUniversity of North CarolinaChapel HillUSA
  2. 2.Division of Medical GeneticsChildren’s Hospital Los AngelesLos AngelesUSA
  3. 3.Department of Pediatrics, Keck School of MedicineUSCLos AngelesUSA
  4. 4.Department of Gastroenterology and HepatologyMedical College of WisconsinMilwaukeeUSA