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AB0024 Genetic association of interleukin-1 beta (-511C/T), interleukin-1 receptor antagonist (IL-1RN) and osteopontin (9250 C/T) polymorphisms with bone mineral density and osteoporosis in russian postmenopausal women
  1. M. Krylov,
  2. N. Tortoptsova,
  3. O. Nikitinskaya,
  4. E. Samarkina,
  5. T. Korotkova,
  6. V. Maykotkin,
  7. L. Benevolenskaya
  1. Institute of Rheumatology, Moscow, Russian Federation

Abstract

Background and objectives Osteoporosis (OP) is a common disease of elderly, in which the immune system plays a critical role in the pathophysiology of postmenopausal OP. Estrogen deficiency induces mild increase in production of proinflammatory cytokines which promotes osteoclastogenesis in the bone marrow. Intermittent PTH treatment increases cancellous bone mass in OP patients. Molecular mechanisms for anabolic PTH actions are largely unknown. Because it regulates expression of osteopontin (OPN) in osteoblasts, OPN could be one targets of PTH in bone.

Objectives We studied the genetic associations between bi-allelic polymorphism (-511C/T) of IL-1b, 86 bp VNTR polymorphism IL-1RN and (9250 C/T) polymorphism OPN and bone mineral (BMD) values in postmenopausal women.

Methods OP was diagnosed by DXA method. The study included 175 women with a diagnosed BMD T-score lower than -2.5 SD (mean:-3.01±0.76) and 212 postmenopausal healthy controls (HC) with a BMD T-score greater -2.5 SD (mean: - 0.30±0.75). Gene polymorphisms were analyzed by PCR-RFLP.

Results IL-1b (-511C/T) and OPN (9250 C/T) polymorphisms were significantly associated with OP. IL-1b (-511CT) and OPN (9250CC) were associated with high risk of OP [OR=1.62, CI (1.06-2.48), p=0,018 and OR=1.87, CI (1.10-3.18), p=0,014 Mantel-Haenzel, correspondingly]. Among the women with OP, the BMD values were significantly lower in the carriers of the IL-1b TT genotype compared with the CC genotype (0.679±0.048 vs.0.743±0.087 p=0.03) for the lumbar spine. The BMD values were significantly lower in the carriers of the OPN CT genotype compared with the TT genotype (0.703±0.069 vs. 0.740±0.088, p=0,04 Mantel-Haenzel). There were no statistically significant associations between the IL-1RN genotypes and BMD values in the OP women.

Conclusions These results suggest that the pathogenesis of OP is associated with IL-1b (-511C/T) and OPN (9250C/T) polymorphisms in postmenopausal Russian women.

Disclosure of Interest None Declared

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