ORIGINAL ARTICLE Pe´ter Rass Ange´la Pa´ kozdi Pe´ ter Lakatos Erika Zilahi Sa´ndor Sipka Gyula Szegedi Zolta´n Szekanecz Vitamin D receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis Received: 10 February 2005 / Accepted: 24 December 2005 Ó Springer-Verlag 2006 Abstract Rheumatoid arthritis (RA) is commonly asso- ciated 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 sec- ondary 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. Keywords Rheumatoid arthritis Osteoporosis Gene polymorphism Vitamin D receptor 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 Introduction Rheumatoid arthritis (RA) is often associated with sec- ondary osteopenia/osteoporosis (OP), which may be observed in 60–80% of the patients [1–5]. Genetic fac- tors have been implicated in the pathogenesis of both RA and OP. In addition, several polymorphisms have been described in genes with importance for the devel- opment of RA or OP [6–12]. In RA, polymorphisms in genes of pro-inflammatory cytokines, cytokine antago- nists, various chemokines, tumor antigens and regula- tory proteins have been investigated [reviewed in 6–8]. 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.). P. Rass A. Pa´kozdi E. Zilahi Z. Szekanecz (&) Division of Rheumatology, Third Department of Medicine, University of Debrecen Medical and Health Science Center, 22 Mo´ricz street, 4004 Debrecen, Hungary E-mail: szekanecz@iiibel.dote.hu Tel.: +36-52-311087 Fax: +36-52-414489 S. Sipka P. Rass E. Zilahi Regional Laboratory of Immunology, Third Department of Medicine, University of Debrecen Medical and Health Science Center, Debrecen, Hungary P. Lakatos First Department of Medicine, Semmelweis University, Budapest, Hungary G. Szegedi Autoimmune Disease Research Group, Hungarian Academy of Sciences, Debrecen, Hungary Rheumatol Int (2006) DOI 10.1007/s00296-006-0106-7