MDR1 C3435T polymorphism is predictive of later onset of ulcerative colitis in Japanese.
Recently, a silent polymorphism of C3435T of the MDR1 gene, encoding the multidrug resistant transporter MDR1/P-glycoprotein, has been found to be associated with susceptibility to ulcerative colitis (UC), but this remains controversial. This study was conducted to find a possible reason for the discrepancies, and it was suggested that the age of onset was important for the association, namely, C3435T was predictive of susceptibility to later onset UC, but not for early onset UC. Linkage disequilibrium of C3435T with T-129C, C1236T and G2677A, T was suggested to be altered in UC, but the analysis of their haplotype provided no advantage in terms of prediction over that with only C3435T. The effect of C3435T on susceptibility could not be explained by that on mRNA expression in rectal mucosa, but it was greater in the C(3435)-noncarriers in the early onset group, allowing the individualization of steroid-based pharmacotherapy.
Osuga
Tatsuya
T
Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Sakaeda
Toshiyuki
T
Nakamura
Tsutomu
T
Yamada
Toshio
T
Koyama
Tatsuya
T
Tamura
Takao
T
Aoyama
Nobuo
N
Okamura
Noboru
N
Kasuga
Masato
M
Okumura
Katsuhiko
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D044466:Asian People / Q000235:genetics; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012007:Rectum / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger