Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease.
The inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis, are chronic inflammatory disorders of the digestive tract. The pathogenesis of IBD is complicated, and it is widely accepted that immunologic, environmental and genetic components contribute to its etiology. To identify genetic susceptibility factors in CD, we performed a genome-wide association study in Japanese patients and controls using nearly 80,000 gene-based single nucleotide polymorphism (SNP) markers and investigated the haplotype structure of the candidate locus in Japanese and European patients. We identified highly significant associations (P = 1.71 x 10(-14) with odds ratio of 2.17) of SNPs and haplotypes within the TNFSF15 (the gene encoding tumor necrosis factor superfamily, member 15) genes in Japanese CD patients. The association was confirmed in the study of two European IBD cohorts. Interestingly, a core TNFSF15 haplotype showing association with increased risk to the disease was common in the two ethnic groups. Our results suggest that the genetic variations in the TNFSF15 gene contribute to the susceptibility to IBD in the Japanese and European populations.
Yamazaki
Keiko
K
Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Japan.
McGovern
Dermot
D
Ragoussis
Jiannis
J
Paolucci
Marta
M
Butler
Helen
H
Jewell
Derek
D
Cardon
Lon
L
Takazoe
Masakazu
M
Tanaka
Torao
T
Ichimori
Toshiki
T
Saito
Susumu
S
Sekine
Akihiro
A
Iida
Aritoshi
A
Takahashi
Atsushi
A
Tsunoda
Tatsuhiko
T
Lathrop
Mark
M
Nakamura
Yusuke
Y
D000328:Adult; D044466:Asian People; D016022:Case-Control Studies; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D006113:United Kingdom
C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha