Haplotype of prostaglandin synthase 2/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease.
OBJECTIVE
Prostaglandin G/H synthase 2 (PTGS2 or COX2) is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases (IBD). In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD.


METHODS
We have genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTGS2 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5' exonuclease assay (TaqMan). New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing.


RESULTS
Allele 5209G was weakly associated with Crohn's disease (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.03-2.57), and allele 8473T with ulcerative colitis (OR 1.50, 95%CI 1.00-2.27). The haplotype including both alleles showed a strong association with IBD (OR 13.15, 95%CI 3.17-116.15). This haplotype, while rare (-0.3%) in the general population, is found more frequently in the patients (3.5%).


CONCLUSIONS
Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.
Cox
David-G
DG
Genome Analysis Team (GAN), International Agency for Research on Cancer, 150 cours Albert Thomas, F-69372 Lyon Cedex 08, France.
Crusius
J-Bart-A
JB
Peeters
Petra-H-M
PH
Bueno-de-Mesquita
H-Bas
HB
Pena
A-Salvador
AS
Canzian
Federico
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000235:genetics; D003424:Crohn Disease / Q000201:enzymology / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide
D004247:DNA; D051546:Cyclooxygenase 2