Crohn's disease and ulcerative colitis share genetic risk variants

Last Updated: 2008-05-02 13:40:08 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Two independent research teams have identified several genetic polymorphisms shared by ulcerative colitis and Crohn's disease.

Both teams, one in the UK and the other in Germany, studied Crohn's disease-associated loci to test for ulcerative colitis associations. According to their reports published online on April 27 by Nature Genetics, Crohn's disease single nucleotide polymorphisms (SNPs) had been identified in previous genome-wide association studies, but no genome-wide association studies have been conducted for ulcerative colitis.

Dr. Stefan Schreiber, at University Hospital Schleswig-Holstein in Kiel, Germany, and colleagues genotyped DNA from 1103 individuals with ulcerative colitis, 1850 individuals with Crohn's disease and 1817 healthy controls. Their analysis included 53 known SNPS as well as close to 100 tagging SNPs for the IRGM, NKX2-3, and PTPN2 gene regions.

Some variants in 3p21.31, NKX2-3, and CCNY turned out to be general inflammatory bowel disease susceptibility loci, observed in both Crohn's disease and ulcerative colitis. Three other affected genes - HERC2, STAT3 and PTPN2 - exhibited associations only with ulcerative colitis.

Dr. Schreiber's team also replicated several Crohn's disease susceptibility regions, although in some cases "it remains unclear which gene in specific regions is associated with the disease."

Meanwhile, UK researchers led by Dr. Jack Satsangi at the University of Edinburgh conducted a nonsynonymous SNP scan in three cohorts, totalling 2987 cases and 4494 controls.

They identified a previously unknown variant in the ECM1 gene that appears to be specific to ulcerative colitis. "ECM1 is a plausible candidate gene for ulcerative colitis," they say, as it encodes extracellular matrix protein 1, which is expressed in small and large intestine, interacts with the basement membrane, and is a strong activator of a key immune regulator.

Dr. Satsangi's group also identified NKX2-3 as a shared susceptibility locus, along with MST1 ("known to suppress cell-mediated immunity by down-regulating interleukin-12") and genes encoding HLA and interleukin-12 and -23, associated with autoimmune diseases.

In contrast to the findings of Dr. Schreiber's team, however, the UK researchers found that PTPN2 is only associated with Crohn's disease.

"The ultimate goal" of this work, writes the German team, is "a systems-biology based high-resolution 'genetic risk map' of Crohn's disease and ulcerative colitis that would guide diagnostic and therapeutic strategies for these debilitating disorders."

Nat Genet 2008