Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese.
OBJECTIVE
To examine an association between the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis (UC) and Crohn's disease (CD) in the Japanese.


METHODS
We studied 108 patients with UC, 79 patients with CD, and 200 sex-matched healthy controls, with respect to three single nucleotide polymorphisms (SNPs) in CTLA4, such as C-318T in the promoter region, A+49G in exon 1 and G+6230A in the 3' untranslated region (3'-UTR) by a PCR-restriction fragment length polymorphism method, and to an (AT)(n) repeat polymorphism in 3'-UTR by fragment analysis with fluorescence-labeling on denaturing sequence gels. Frequency of alleles and genotypes and their distribution were compared statistically between patients and controls and among subgroups of patients, using chi (2) and Fisher exact tests.


RESULTS
The frequency of "A/A" genotype at the G+6230A SNP site was statistically lower in UC patients than in controls (3.7% vs 11.0%, P = 0.047, odds ratio (OR) = 0.311). Moreover, the frequency of "G/G" genotype at the A+49G SNP site was significantly higher in CD patients with fistula (48.6%) than those without it (26.2%) (P = 0.0388, OR=2.67).


CONCLUSIONS
The results suggest that CTLA4 located at 2q33 is a determinant of UC and responsible for fistula formation in CD in the Japanese.
Machida
Haruhisa
H
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
Tsukamoto
Kazuhiro
K
Wen
Chun-Yang
CY
Narumi
Yukiko
Y
Shikuwa
Saburou
S
Isomoto
Hajime
H
Takeshima
Fuminao
F
Mizuta
Yohei
Y
Niikawa
Norio
N
Murata
Ikuo
I
Kohno
Shigeru
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human