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Haplotypes of PADI4 susceptible to rheumatoid arthritis are also associated with ulcerative colitis in the Japanese population.

Chen CC, Isomoto H, Narumi Y, Sato K, Oishi Y, Kobayashi T, Yanagihara K, Mizuta Y, Kohno S, Tsukamoto K

Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disorder characterized by intractable inflammation specific to the gastrointestinal tract. The precise etiology of IBD remains unknown. Recently, haplotypes of peptidylarginine deiminase type 4 (PADI4) have been identified as the rheumatoid arthritis (RA)-susceptible gene. PADI4 is located at 1p36, which is one of chromosomal loci susceptible for IBD. Then, we examined whether haplotypes and diplotypes of PADI4 are associated with IBD in the Japanese population. We studied haplotypes of PADI4 in 114 patients with UC, 83 patients with CD, and 200 gender-matched healthy controls by PCR-restriction fragment length polymorphism. Frequencies and distributions of haplotypes and diplotypes were compared statistically between patients and controls by logistic regression analysis. The frequency of haplotype 1 was significantly decreased in patients with UC, compared to that in controls (P=0.037; odds ratio (OR)=0.702). In contrast, the frequency of haplotype 2 in patients with UC was significantly higher than that in controls (P=0.003; OR=1.722). Moreover, of a total of 114 patients with UC, 15 (13.2%) had a diplotype homozygous for haplotype 2, the frequency being significantly higher than in controls (9/200, 4.5%; P=0.008, OR=3.215). Our results indicate that haplotype 1 of PADI4 is associated with non-susceptibility to UC, whereas haplotype 2 is susceptible to UC. Thus, it is likely that PADI4 is one of genetic determinants of UC in the Japanese population.

Published 14 January 2008 in Clin Immunol, 126(2): 165-71.
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