Diverticular Disease: Genetics and Collagen

Compared with other diseases, advancements in science and technology left diverticular disease (DD) behind decades ago. Worldwide occurrence, poor quality of life, level of mortality and healthcare costs should have generated far more research effort. Preoccupation with dietary fibre levels, constipation and ageing has and still is stunting research. Fibre levels have benefits for constipation and symptoms but research into cause, prevention and other treatments has been overtaken by the necessary investigations into the surgical rescue of DD effects. Recently valid trials and surveys have disputed traditional thinking about a dietary cause and revealed a genetic factor.

Studies using twins ( 1 ) suggested that inheritability accounted for 40% of the odds of getting DD, with the non-shared environment effect at 60%. Another study estimated that 53% of susceptibility to DD resulted from genetic factors. Compared with the general population at 1.0, the relative risk for DD was 2.92 in siblings, 14.5 for identical twins and 5.5 for twins not identical. Gender altered the results for identical twins, females having a stronger association ( 2 ).

This does not mean that DD is an inherited disease transferable through generations. Times and locations of the appearance of DD in the world – it’s epidemiology – ( 3 ) refute this possibility. DD does not follow any known patterns of inheritance. However the effects of the same environment in a family circle and its generations cannot be discounted, “environment” in this context refers to substances which can enter the body from the outside by eating, drinking, breathing and through the skin or internal surfaces.

A combination of genetics and environment is a known cause of diseases. While personal genetics can not be changed, environmental change is possible in individuals, families and cultures. How an individual’s make-up enables them to deal with their environment is the likely basis for susceptibility to DD. This is illustrated when the DD risk can change on immigration and a different lifestyle. On the other hand, who gets side effects from a drug is an example of the same environment but genetic differences in the drugs metabolism and clearance from the body.

Genetic diseases from inherited or rogue genes are rare but those which result in defects in collagen formation and structure have increased incidence of colon diverticular disease ( 4-9 ). This occurs in adolescents and young adults, a pattern distinct from the progressive incidence of DD with ageing. Collagen, in connective tissue, has widespread functions in the body of supporting other structures and their flexibility, for example, in the walls of blood vessels and the digestive organs, and in the skin and joints. As a consequence such genetic diseases can affect many parts of the body. The finding of DD in a younger person should lead to a search for an underlying genetic disease ( 10 ). Alternatively, abdominal pain in a younger person with a collagen related genetic disease should be investigated for DD complications ( 4 ).

The presence of diverticula i.e. diverticulosis, is the diagnostic criterion for DD. An environmental contribution to their formation has not received much investigation and would likely be a slower process than a genetic effect. The diverticula have already formed when symptoms or cancer screening prompt colon investigation in older people. More recent investigations show increases in 30 – 40 year old patients, particularly in Hispanic men in an American survey ( 11 ). An age distinction between the influence of genetic and environmental factors may not be clean cut.

Examination of tissues, commonly from older people, show changes in the collagen components of the colon wall. There are changes in the level of enzymes which should maintain stable collagen structure ( 12 ). This results in decreased levels of mature collagen type 1 with increased levels of cross-linked collagen type 111 ( 13 ). Elastin, a type of collagen, is deposited within the colon wall muscles ( 14 ). There is remodelling of the colon structure with thickened, shortened longitudinal muscles and more rigid, less elastic walls in affected parts of the colon. Such physical changes must affect the ability of the colon in its movements to process and eliminate its contents. Pressure levels inside the damaged colon could easily result in herniation through weak places and thus the formation of diverticula. Faulty collagen in the colon structure appears a pre-requisite for diverticular formation at any age, even in long colons ( 6 ).

In addition to the damaged structure in older people, there are profound changes to the nerve control of the colon which might precede the structural changes ( 15 ). The parasympathetic system which controls normal function of the colon is affected in two ways. The cholinergic ( 16 ) and nitergenic (17 ) responses of contraction and relaxation are changed so that movements of the colon are less coordinated. The seratogenic system is also compromised ( 18 ) and other neurotransmitters do not always have a normal effect on a colon with DD. The structural and nerve damage could be caused by the environment factor of smoking western cigarettes which has only recently received research attention. Genetics have a role in individual and ethnic differences in dealing with this environment ( 19 ).

There is no doubt that ageing and diet affect symptoms which lead to examinations and the discovery of diverticula on the colon and a diagnosis. Colon screening can find DD without symptoms. DD is a complicated disease to fathom in cause and effect, finding diverticula is neither the beginning nor the end of the disease process. Opinion on the cause of DD is moving away from dietary fibre levels to a more scientific basis which hopefully will continue.


1        Granlund J et al. The genetic influence on diverticular disease – a twin study. Aliment Pharmacol Ther. 2012, 35, 1103.

2        Strate LL et al. Heritability and familial aggregation of diverticular disease: a population-based study of twins and siblings. Gastroenterology. 2013, 144, 736.

3        M Griffiths. Diverticular Disease: Updated Epidemiology. on this website.

4        Santin BJ et al. Colonic diverticulitis in adolescents: an index case and associated syndromes. Pediatr Surg Int. 2009, 25, 901.

5        Picchio M et al. Diffuse intestinal diverticulosis: a case report. Acta Chir Belg. 2005, 105, 670.

6        Wassenaar MJ et al. Acromegaly is associated with increased prevalence of colonic diverticula: a case-control study. J Clin Endocrinol Metab. 2010, 95, 2073.

7        Chang MY & Ong AC. Autosomal Dominant Polycystic Kidney Disease: Recent Advances in Pathogenesis and Treatment. Nephron Physiol. 2007, 108, 1.

8        Stover DG et al. Diverticulitis in a Young Man with Hyper IgE Syndrome. South Med J. 2010, 103, 1261.

9        Commane DM et al. Diet, ageing and genetic factors in the pathogenesis of diverticular disease. World J Gastroenterol. 2009, 15, 2479.

10    Defuentes G et al, Right diverticular colitis revealing an Ehlers-Danlos syndrome. Presse Med. 2004, 33, 1591.

11    Kijsirichareanchai K et al. Diverticulitis in the young. J Prim Care Community Health. 2015, 6, 29.

12    Mimura T et al. Up-regulation of collagen and tissue inhibitors of matrix metalloproteinase in colonic diverticular disease. Dis Colon Rectum. 2004, 47, 371.

13    Stumf M et al. Increased distribution of collagen type 111 and reduced expression of  matrix metalloproteinase 1 in patients with diverticular disease. Int J Colorectal Dis. 2001, 16, 271.

14    Vermeulen J et al. Pathophysiology and prevention of diverticulitis and perforation. Neth J Med. 2010, 68, 303.

15    Gallego D et al. Invitro motor patterns and electrophysiological changes in patients with colonic diverticular disease. Int J Colorectal Dis. 2013, 28, 1413.

16    Golder M et al. Smooth muscle cholinergic denervation hypersensitivity in diverticular disease. Lancet, 2003, 361, 1945.

17    Espin F et al. Nitergic neuro-muscular transmission is up-regulated in patients with diverticulosis. Neurogastroenterol Motil. 2014, 26, 1458.

18    Bottner N et al. The enteric serotonergic system is altered in patients with diverticular disease. Gut, 2013, 62, 1753.

19    M Griffiths. Cigarette Smoking: The Cause of Diverticular Disease? on this website

© Mary Griffiths 2015.

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