Characteristics of Japanese inflammatory bowel disease susceptibility loci.
BACKGROUND
There are substantial differences in inflammatory bowel disease (IBD) genetics depending on the populations examined. We aimed to identify Japanese population-specific or true culprit susceptibility genes through a meta-analysis of past genetic studies of Japanese IBD.


METHODS
For this study, we reviewed 2,703 articles. The review process consisted of three screening stages: we initially searched for relevant studies and then relevant single nucleotide polymorphisms (SNPs). Finally, we adjusted them for the meta-analysis. To maximize our chances of analysis, we introduced proxy SNPs during the first stage. To minimize publication bias, no significant SNPs and solitary SNPs without pairs were combined to be reconsidered during the third stage. Additionally, two SNPs were newly genotyped. Finally, we conducted a meta-analysis of 37 published studies in 50 SNPs located at 22 loci corresponding to the total number of 4,853 Crohn's disease (CD), 5,612 ulcerative colitis (UC) patients, and 14,239 healthy controls.


RESULTS
We confirmed that the NKX2-3 polymorphism is associated with common susceptibility to IBD and that HLA-DRB1*0450 alleles increase susceptibility to CD but reduce risk for UC while HLA-DRB1*1502 alleles increase susceptibility to UC but reduce CD risk. Moreover, we found individual disease risk loci: TNFSF15 and TNFα to CD and HLA-B*5201, and NFKBIL1 to UC. The genetic risk of HLA was substantially high (odds ratios ranged from 1.54 to 2.69) while that of common susceptibility loci to IBD was modest (odds ratio ranged from 1.13 to 1.24).


CONCLUSIONS
Results indicate that Japanese IBD susceptibility loci identified by the meta-analysis are closely associated with the HLA regions.
Department of Gastroenterology, Rheumatology, and Clinical Immunology, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan, arimura@sapmed.ac.jp.
Yoshiaki
Y
Arimura
Hiroyuki
H
Isshiki
Kei
K
Onodera
Kanna
K
Nagaishi
Kentaro
K
Yamashita
Tomoko
T
Sonoda
Takayuki
T
Matsumoto
Atsushi
A
Takahashi
Masakazu
M
Takazoe
Keiko
K
Yamazaki
Michiaki
M
Kubo
Mineko
M
Fujimiya
Kohzoh
K
Imai
Yasuhisa
Y
Shinomura
D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D020641:Polymorphism, Single Nucleotide