rs1004819 Is the Main Disease-Associated IL23R Variant in German Crohn's Disease Patients: Combined Analysis of IL23R, CARD15, and OCTN1/2 Variants

被引：119

作者：

Glas, Juergen ^{[1
,2
]}

Seiderer, Julia ^{[1
]}

Wetzke, Martin ^{[1
,2
]}

Konrad, Astrid ^{[1
]}

Toeroek, Helga-Paula ^{[1
]}

Schmechel, Silke ^{[1
]}

Tonenchi, Laurian ^{[2
]}

Grassl, Christine ^{[2
]}

Dambacher, Julia ^{[1
]}

Pfennig, Simone ^{[1
]}

Maier, Kerstin ^{[2
]}

Griga, Thomas ^{[4
]}

Klein, Wolfram ^{[5
]}

Epplen, Joerg T. ^{[5
]}

Schiemann, Uwe ^{[6
]}

Folwaczny, Christian ^{[3
]}

Lohse, Peter ^{[7
]}

Goeke, Burkhard ^{[1
]}

Ochsenkuehn, Thomas ^{[1
]}

Mueller-Myhsok, Bertram ^{[8
]}

Folwaczny, Matthias ^{[2
]}

Mussack, Thomas ^{[3
]}

Brand, Stephan ^{[1
]}

机构：

[1] Univ Munich, Dept Med Grosshadern 2, Munich, Germany

[2] Univ Munich, Clin Prevent Dent & Parodontol, Munich, Germany

[3] Univ Munich, Dept Surg, Munich, Germany

[4] Knappschaftskrankenhaus Dortmund, Dept Internal Med, Dortmund, Germany

[5] Ruhr Univ Bochum, Dept Human Genet, Bochum, Germany

[6] Inselspital Bern, Dept Gen Internal Med, CH-3010 Bern, Switzerland

[7] Univ Munich, Inst Clin Chem Grosshadern, Munich, Germany

[8] Max Planck Inst Psychiat, D-80804 Munich, Germany

来源：

PLOS ONE | 2007年 / 2卷 / 09期

关键词：

D O I：

10.1371/journal.pone.0000819

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background. The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants. Methods. Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C -> T) and SLC22A5/OCTN2 (-207 G -> C). Results. All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11); OR 1.56; 95 % CI (1.37-1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [P = 8.04x10(-8); OR 0.43; CI (0.31-0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. Conclusion. IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p. Arg381Gln IL23R variant is a protective marker for CD and UC.

引用

页数：8

共 53 条

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