Polymorphism of the heat-shock protein gene Hsp70-2, but not polymorphisms of the IL-10 and CD14 genes, is associated with the outcome of Crohn's disease.
OBJECTIVE
In Crohn's disease (CD) a Th-1 dominant immune reaction is induced, which could be associated with genetic predisposition. Several previous studies have investigated the roles of CD14, heat-shock protein (Hsp)70 and IL-10 gene polymorphisms in the development of the disease. The results are contradictory and inter-racial differences are implicated. Therefore, this phenomenon was evaluated in well-documented Caucasian patients with CD in order to verify the clinical importance of these polymorphisms.


METHODS
The genomic DNA of 133 patients with CD and that of 75 healthy controls were examined. CD was divided into subgroups according to the Vienna classification. An arbitrary classification system based on disease severity was also applied, which was determined according to the therapeutic intervention. The CD14 (-159 C-->T) promoter gene polymorphism was investigated by melting-point analysis. The IL-10 (-1082 G-->A) and Hsp70-2 (1267 A-->G) gene polymorphisms were detected by RFLP (restriction fragment length polymorphism).


RESULTS
None of the allele frequencies of the examined polymorphisms differed significantly between the patient and control populations. Neither the CD14 nor the IL-10 polymorphisms exhibited any correlation with the development or with the progression of the disease. With regard to Hsp70-2 gene polymorphism, those patients who carry at least one A allele have a significantly lower probability of the need for surgical intervention.


CONCLUSIONS
Allele A of the Hsp70-2 gene may be associated with a less severe form of CD, suggesting the clinical value of the genotype assessment. The genetic determination of the defense mechanisms in CD appears to be associated with the polymorphism of the Hsp70-2 gene rather than that of the CD14 or IL-10 genes.
Klausz
Gergely
G
Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Molnár
Tamás
T
Nagy
Ferenc
F
Gyulai
Zsófia
Z
Boda
Krisztina
K
Lonovics
János
J
Mándi
Yvette
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics
D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D018950:Lipopolysaccharide Receptors; D016753:Interleukin-10