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Vitamin D receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis

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Abstract

Rheumatoid arthritis (RA) is commonly associated with decreased bone mineral density (BMD) due to numerous factors. BsmI polymorphism of the vitamin D receptor (VDR) gene has been implicated in the pathogenesis of osteoporosis. Vitamin D has several immunomodulatory effects and thus may play a role in the course of arthritis. However, little data is available on the possible relationship between RA and VDR gene polymorphisms. In this study, the frequency of BsmI polymorphism genotypes were compared with that found in other countries. In this study, 64 RA patients and 40 healthy controls were tested for VDR gene BsmI polymorphism genotypes. Frequencies of B and b alleles were associated with markers of bone metabolism and RA. Among control subjects, the frequency of the BB genotype is relatively high (27.5%). In RA with secondary osteopenia/osteoporosis the BB genotype was more rare, the bb was more common than in control subjects. Markers of bone metabolism were associated with the B allele. RA patients carrying the B allele had lower BMD and increased bone loss over 1 year. The B allele was also correlated with increased osteoclast and osteoblast function, as determined by the assessment of biochemical markers of bone metabolism. Rheumatoid factor titer, which is an independent marker for disease progression in RA, was higher in bb patients. Our data suggest, that the imbalance in B and b allele expression may be involved in the pathogenesis of RA-associated osteoporosis. The possible involvement of vitamin D and VDR gene polymorphisms in the development and progression of RA needs further elucidation.

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Abbreviations

BMD:

Bone mineral density

CRP:

C reactive protein

DEXA:

Dual energy X-ray absorptiometry

DNA:

Deoxyribonucleic acid

DPYD:

Deoxy-pyridinolin

ESR:

Erythrocyte sedimentation rate

IL:

Interleukin

OC:

Osteocalcin

OP:

Osteoporosis

PCR:

Polymerase chain reaction

RA:

Rheumatoid arthritis

RF:

Rheumatoid factor

TNF:

Tumor necrosis factor

VAS:

Visual analogue scale

VDR:

Vitamin D receptor

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Acknowledgements

We thank our colleagues at the Regional Immunological Laboratory of the third Department of Medicine for the assessment of biochemical markers and cytokines, and the staff of the Bone Densitometry Lab at the Department of Obstetrics and Gynecology for the DEXA evaluations. We also thank Katalin Hodosi for the statistical analysis and Dr. Imre Semsei for his help in the molecular biology techniques.

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Correspondence to Zoltán Szekanecz.

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Financial support: ETT 314/96 and ETT 60/2001 grants from the Medical Research Council of Hungary (Z.S.), and FKFP 18/2000 grant from the Research and Development in Highest Education Council (Z.S.).

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Rass, P., Pákozdi, A., Lakatos, P. et al. Vitamin D receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis. Rheumatol Int 26, 964–971 (2006). https://doi.org/10.1007/s00296-006-0106-7

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