Heat-shock protein HSP70-2 genotypes in patients with Crohn's disease: a more severe clinical course with intestinal complications in presence of the PstI-polymorphism.
BACKGROUND
70 kDa Heat shock proteins are involved in mucosal protecting reactions in the gut of patients with inflammatory bowel disease. Recently, a single nucleotide polymorphism (PstI, nucleotide 1267) was associated with intestinal perforations and formation of abscesses and fistulas in Japanese patients with Crohn's disease. Our purpose was to evaluate this phenomenon in Caucasian patients with Crohn's disease and to verify the clinical importance of this polymorphism.


METHODS
61 consecutive patients with Crohn's disease and 61 healthy control persons were examined. After DNA extraction and PCR amplification spanning the PstI-site, restriction fragment length polymorphism analyses (RFLP) were performed. Homozygous and heterozygous genotypes (AA, AB, BB) were then correlated with the clinical characteristics of the patients, especially with their intestinal complications.


RESULTS
Intestinal perforations and formation of fistulas, abscesses and conglomerate tumors were significantly associated with allele B (p = 0.04). Patients with genotype BB showed the highest prevalence for surgical interventions (82%), whereas patients with genotype AA had the lowest prevalence (56%). Onset of disease, the need for immunosuppressive therapy and the occurrence of extraintestinal manifestations did not differ between the three genotypes. Allele A was significantly associated with combined involvement of ileum and colon.


CONCLUSIONS
Caucasian patients carrying the HSP70-2 PstI-polymorphism seem to have a more severe form of Crohn's disease (perforations, abscesses, fistulas, conglomerate tumors). Especially, the homozygous genotype (BB) predisposes for a clinical course with high risk of surgical intervention.
Medizinische Poliklinik, Klinikum der Universität - Innenstadt, Ludwig-Maximilians-Universität München, Germany.
J
J
Debler
U
U
Schiemann
U
U
Seybold
T
T
Mussack
N
N
Landauer
R
R
Ladurner
M
M
Gross
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003424:Crohn Disease / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index
D018840:HSP70 Heat-Shock Proteins