Investigating the Genetic Architecture of Orofacial Granulomatosis (OFG).

Crohn's disease (CD), aninflammatory disease ofthe gut, results from aninteraction between normal gut bacteria and an immune system disrupted by genetic and environmental factors. In some individuals, CD affects the mouth causing cracked swollen lips and painful ulceration. This pattern often strikes in teenagers and has a major negative impact on patient's selfesteem.
Oral CD is also referred to as orofacial granulomatosis (OFG) andcanoccur alone or incombination with CD inthe gut.OFG is unique from CD in that80% of patients also have atopy (hayfever, asthma). Moreover, about 60% of cases respond to diets which remove preservatives and colourings.
The group's active research program over several years has made significant steps toward understanding the pathogenesis of OFG. We are now focussing on the genetics of OFG and how this compares to the genetics of CD with particular interest in bacteria-immune interaction Previous work included;
* performing a Genome Wide Association Study (GWAS) of the following:
OFG vs. UC: 248 cases, 3591 controls
OFG vs. CD: 248 cases, 3192 controls
GWAS detected 2 SNPs with suggestive significance that need to be followed up
* Screening the coding regions oftheNOD2 gene for rare, potentially pathogenic variants in 198 OFG patients identified a number of novel rare variants in OFG patients.
* Analysis of the oral Microbiome of100 OFG patients, 50 Crohn's disease and 50 healthy controls showed that there was an evidence of global differences between OFG patients and controls.
* Genotyping of risk variants inNOD2, IRGM, IL23R, ATG16L1 (CD), BTNL2 (sarcoidosis), and FLG (atopy) in 201 OFG only and concurrent intestinal CD patients and 1023 healthy controls suggested that genetic variants of NOD2 are only associated with OFG in patients with concurrent intestinal disease.