Study of chromosomal region 5p13.1 in Crohn's disease, ulcerative colitis, and rheumatoid arthritis.
Chromosomal region 5p13 includes regulatory elements of the prostaglandin receptor EP4 (PTGER4) gene and is associated with inflammatory bowel disease (IBD) susceptibility. We aimed at corroborating the association of the PTGER4 risk variant in IBD. Given the proinflammatory activity of prostaglandin E(2) in rheumatoid arthritis (RA), the reduction in incidence and severity of collagen-induced arthritis observed in mice deficient in the prostaglandin receptor EP4, and a modest signal of association found in an RA genome-wide scan, we proposed to extend the investigation of this locus to RA patients. A total of 709 Crohn's disease (CD) patients, 662 ulcerative colitis (UC) patients, and 1369 control subjects were genotyped for rs17234657. This polymorphism was also analyzed in 605 RA patients, and rs6871834 was studied in the RA patient group. Replication of the previous finding in CD was achieved in our independent collections, although with a milder effect (odds ratios = 1.23) than that originally described. No further association of the previously mentioned polymorphisms was detected with either UC or RA patients. We validated this 5p13 signal as a genuine susceptibility factor for CD in Caucasian populations. Our data seem to rule out a major influence of these polymorphisms on UC or RA predisposition.
Perdigones
Nieves
N
Immunology Department, Hospital Clínico, San Carlos, Madrid, Spain.
Martín
Ezequiel
E
Robledo
Gema
G
Lamas
José Ramón
JR
Taxonera
Carlos
C
Díaz-Rubio
Manuel
M
de la Concha
Emilio G
EG
López-Nevot
Miguel Angel
MA
García
Antonio
A
Gómez-García
María
M
Fernández-Gutiérrez
Benjamín
B
Martín
Javier
J
Urcelay
Elena
E
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016009:Chi-Square Distribution; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018078:Receptors, Prostaglandin E / Q000235:genetics*; D058309:Receptors, Prostaglandin E, EP4 Subtype
C545650:PTGER4 protein, human; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype