Crohn’s disease: “back to the future”

Vito Annese

Endoscopy & IBD Units, IRCCS-CSS Hospital San Giovanni Rotondo (Italy) E-mail: v.annese@operapadrepio.it

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• Gastroenterology

Dear Sirs,

we read with interest the letter by El-Tawil suggesting “A new hypothesis on inflammatory bowel disease”. Basically, extrapolating the absence of symptoms of Crohn’s disease in “healthy” relatives with one or even two NOD2 risk alleles after 5-8 years of follow-up described in our series1, he argued that environmental factors might influence genetic markers throughout generation. In other words i.e. infections might have influenced during the 18th or beginning of 19th centuries a natural selection, predisposing the progeny of survivors to autoimmune disease, i.e. IBD or rheumatoid arthritis. This hypothesis is indeed not “new” and have already put forward in Crohn’s disease (see i.e. so called “cold chain hypothesis”2, or “hygiene hypothesis”3-4. No scientific prove is available yet, but similar suggestions, in the context of so called evolutionary medicine, have been proposed also for diabetes5 and blood hypertension6, and are absolutely plausible.
The paradox of complex disease like Crohn’s disease is that the discovery of genetic predisposing factors is rapidly increasing (at least 32 loci identified so far, although still explaining the minority of estimated genetic predisposition7, but the identification of environmental trigger factors is sticky8. Therefore, without more “complaining” of the past (i.e. genetic predisposition), we should perhaps greater concentrate on the present and future.

References

1)    Annese V, Latiano A, Palmieri O, Lombardi G, Andriulli A. NOD2/CARD15 in healthy relatives of IBD patients. Eur Rev Med Pharmacol Sci 2006; 10: 33-36.
2)    Hugot JP, Alberti C, Berrebi D, Bingen E, Cézard JP. Crohn’s disease: the cold chain hypothesis. Lancet 2003; 362: 2012-2015.
3)    Strachan DP. Hay fever, hygiene, and household size. BMJ 1989; 299: 1259-1260.
4)    Yazdanbakhsh M, Kremsner PG, van Ree R. Allergy, parasites, and the hygiene hypothesis. Science 2002;296:490-4.
5)    Swynghedauw B. Evolutionary medicine. Acta Chir Belg 2004; 104: 132-139.
6)    Campbell MC, Tishkoff SA. African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu Rev Genomics Hum Genet 2008; 9: 403-433.
7)    Barrett JC, Hansoul S, Nicolae DL, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 2008; 40(8): 955-962.
8)    Krishnan A, Korzenik JR. Inflammatory bowel disease and environmental influences. Gastroenterol Clin North Am 2002; 31: 21-39.

Vito Annese MD
Endoscopy & IBD Units
IRCCS-CSS Hospital
San Giovanni Rotondo, Italy

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