The cause of the inflammatory bowel diseases (IBD)
ulcerative colitis and Crohn’s disease is not known. However, there is good
evidence to suggest that these diseases are due to a combination of factors,
including genetic predisposition, environmental factors, and alterations in the
function of the immune system. The purpose of this review is to highlight the
important genetic aspects of IBD.
There is strong evidence to suggest a genetic basis
for IBD, including familial clustering and racial and ethnic differences in risk
for IBD. Ten to twenty percent of affected individuals will have family history
of IBD, with the highest risk among first-degree relatives. At this time, a
positive family history is the single-greatest risk factor for IBD, with
relatives of affected individuals having at least a 10-fold increased risk for
IBD.
Increased rates of IBD among identical twins
compared to fraternal twins, and among siblings compared to spouses of affected
individuals, suggests that genetic rather than environmental factors are
primarily responsible for the observed familial aggregation or concentration of
incidence for the disease.
Racial differences in IBD incidence exist, with the
highest rates among Caucasians. Also, there is evidence for ethnic aggregation
of IBD, with higher rates of IBD among those of Jewish descent. Furthermore,
within Jewish populations, rates are higher in Ashkenazi than Sephardic
Jews. These differences occur across different time periods and geographic
areas, suggesting a genetic basis as the most likely explanation for these
findings.
Recently, the first gene associated with Crohn’s
disease, the NOD2 gene, was identified. There is intense ongoing research into
understanding how defects in the NOD2 gene leads to Crohn’s disease and into
finding the other genes that cause IBD (It is likely that there are 4-5 genes
involved).
Finding causative genes will be of great importance in better understanding the
underlying changes that lead to IBD. This could, in turn, be of potential great
benefit in predicting the course of disease in individual patients and in
guiding appropriate medical therapy. Such information also could potentially
allow for identification of family members at risk for developing IBD.