TNFSF15 is an ethnic-specific IBD gene.
BACKGROUND
Inflammatory bowel disease (IBD) is a clinically and, likely, genetically heterogeneous group of disorders. A recent report suggests that genetic variations in the TNFSF15 gene contribute to the susceptibility of IBD in both Japanese and Caucasian populations. The aim was to confirm the association between TNFSF15 high- and low-risk haplotypes and IBD in a Caucasian population.


METHODS
Five single-nucleotide polymorphisms (SNPs) that comprise the 2 common haplotypes were genotyped in 599 Caucasian patients with Crohn's disease (CD), 382 Caucasian patients with ulcerative colitis (UC), and 230 ethnically matched healthy controls, including both Jews and non-Jews.


RESULTS
The previously reported 'risk' haplotype was not associated with CD or UC (88.2% in CD cases versus 88.3% in controls, P = 0.96; 88.1% in UC cases versus 88.3% in controls, P = 0.78). We did, however, observe an increased frequency of the "protective" haplotype in non-Jewish controls for both CD and UC (38.8% CD cases versus 50% controls, P = 0.01; 37.3% UC cases versus 50% controls, P = 0.01) with no such effect observed in the Jewish samples. There was an interactive effect between ethnicity and the protective haplotype in CD (P = 0.04).


CONCLUSIONS
We observed a protective haplotype, consisting of the minor alleles for all 5 markers, to have a higher frequency in the non-Jewish controls than in CD and UC. Of further interest, the haplotype frequency was in the opposite direction in our Jewish case-control panels (both CD and UC), leading us to conclude 1) that TNFSF15 is indeed an IBD susceptibility gene, and 2) the disease susceptibility is ethnic-specific.
Medical Genetics Institute, Cedars-Sinai Medical Center Los Angeles, California, USA.
Yoana
Y
Picornell
Ling
L
Mei
Kent
K
Taylor
Huiying
H
Yang
Stephan R
SR
Targan
Jerome I
JI
Rotter
D000483:Alleles; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D005006:Ethnicity; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000208:ethnology* / Q000235:genetics*; D007585:Jews; D020641:Polymorphism, Single Nucleotide; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics*; D044465:White People / Q000235:genetics
C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15