Allelic variation at the interleukin 1beta gene is associated with decreased bone mass in patients with inflammatory bowel diseases.
BACKGROUND
Interleukin 1beta (IL-1beta) and its natural antagonist have been implicated in the pathogenesis of inflammatory bowel disease (IBD). Both cytokines influence bone formation. IL-1beta stimulates osteoclast activity while interleukin 1 receptor antagonist (IL-1ra) enhances bone formation.


OBJECTIVE
To determine whether the decreased bone mass in IBD is related to gene polymorphisms coding for IL-1beta and IL-1ra, and thus identify patients with an increased risk.


METHODS
Bone mineral densitometry was performed at the femoral neck, lumbar spine, and the distal third of the radius in 75 IBD patients (34 men/41 women; 40.3 (1.6) years) and in 58 healthy controls (HC; 28 men/30 women; 32.4 (1.2) years). Values were correlated with the TaqI and AvaI gene polymorphisms in the IL1B and the variable number of tandem repeats gene polymorphism in the IL1RN gene.


RESULTS
In IBD patients, but not in HC, carriers of allele 2 at the AvaI gene polymorphism (IL1B-511*2) had significantly lower Z scores at the lumbar spine (-0.82 (0.13) v -0.29 (0.21) p=0.03) and the femoral neck (-0.59 (0.14) v 0.15 (0.19); p=0.003) than non-carriers. These patients also had a higher risk for osteopenia or osteoporosis at the femoral neck (odds ratio 3.63 (95% confidence interval 0.95-13.93)). No association was found between bone mass and the other gene polymorphisms analysed in IBD patients or in HC.


CONCLUSIONS
Our results suggest that genetic variability may be a major determinant of bone loss in IBD. Carriers of IL1B-511*2, who are hypersecretors of IL-1beta, have a higher risk of presenting with low bone mass in IBD. Screening for this allele may contribute to determination of the risk of bone loss at the time of disease onset.
Nemetz
A
A
2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
Tóth
M
M
García-González
M A
MA
Zágoni
T
T
Fehér
J
J
Peña
A S
AS
Tulassay
Z
Z
D015502:Absorptiometry, Photon; D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D010024:Osteoporosis / Q000235:genetics; D011110:Polymorphism, Genetic; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics; D020080:Tandem Repeat Sequences / Q000235:genetics
D007375:Interleukin-1; D017472:Receptors, Interleukin-1