Risk factors for perianal Crohn's disease: the role of genotype, phenotype, and ethnicity.
OBJECTIVE
Perianal disease (PD) is a frequent complication of Crohn's disease (CD). The lack of association between PD and development of intestinal penetrating disease may suggest that PD is a distinct phenotype with specific genetic or clinical risk factors. This study was undertaken to evaluate the role of genotype, clinical, and demographic characteristics with PD.


METHODS
Phenotypic data on 121 CD patients with PD and 179 patients without PD were carefully characterized. The patients were genotyped for disease-associated OCTN1/2 and NOD2/CARD15 variants and the TNF-alpha promoter polymorphisms. Analysis was performed to evaluate the differences in phenotype and genotype frequencies between the PD group and the non-PD group.


RESULTS
PD was associated with rectal involvement (odds ratio [OR] 2.27, 95% CI 1.32-3.91) and with Sephardic (non-Ashkenazi) Jewish ethnicity (OR 1.71, 95% CI 1.02-2.9). No association was found among the studied OCTN, NOD2, TNF-alpha variants and the risk for PD.


CONCLUSIONS
The strongest factor associated with PD is rectal inflammation. OCTN1/2, NOD2/CARD15, and TNF-alpha promoter variants do not play a role in the risk to PD in the Jewish Israeli population. The association of ethnicity with PD may suggest that there are as yet unknown genetic variants that are associated with PD.
Karban
Amir
A
Departments of Medicine and Gastroenterology, Rambam Medical Center, Haifa, Israel.
Itay
Maza
M
Davidovich
Ofir
O
Leshinsky-Silver
Esther
E
Kimmel
Gad
G
Fidder
Herma
H
Shamir
Ron
R
Waterman
Matti
M
Eliakim
Rami
R
Levine
Arie
A
D001004:Anus Diseases / Q000209:etiology* / Q000235:genetics; D003424:Crohn Disease / Q000150:complications / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D005838:Genotype; D006801:Humans; D007585:Jews; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D010641:Phenotype; D012307:Risk Factors; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha