Vitamin D receptor initiation codon polymorphism, bone density and inflammatory activity of patients with ankylosing spondylitis.
OBJECTIVE
Osteoporosis is a common finding in ankylosing spondylitis (AS) and may contribute to spinal deformity and bone pain. Bone metabolism as well as inflammatory processes are influenced by the vitamin D receptor gene (VDR). We investigated initiation codon ( FokI) and 3'UTR ( BsmI) polymorphisms of the VDR for whether there could be an association with bone mineral density (BMD) in relation to bone metabolism or inflammatory activity in patients with AS.


METHODS
In this study, 104 patients with AS (m/w 71/33, mean age 41+/-12 years) were investigated for their lumbar and femoral BMD by DEXA and in part by QCT measurements and compared to 54 healthy controls. Disease activity indices, serum markers of bone metabolism and inflammation were recorded. FokI and BsmI polymorphisms of the VDR were genotyped using genomic DNA from peripheral leukocytes with present or absent restriction sites defined as alleles " f" and " b" or " F" and " B," respectively.


RESULTS
In male AS patients, FokI genotypes were significantly associated with spinal but not with femoral BMD values ( P=0.01) as independent predictors of low BMD, which was also influenced by BMI, and inflammatory and pain indices. CRP and ESR values were also significantly associated with FokI genotypes. BMD in female patients showed no significant association with either FokI or BsmI genotypes of the VDR.


CONCLUSIONS
This is the first evidence that the VDR gene may be involved in BMD differences, bone metabolism and inflammatory processes in ankylosing spondylitis. A possible interaction of the vitamin D system, cytokines and bone could define new diagnostic and therapeutic implications in ankylosing spondylitis.
Obermayer-Pietsch
Barbara M
BM
Department of Internal Medicine, Division of Endocrinology/Nuclear Medicine, Karl Franzens University, Auenbruggerplatz 15, 8036, Graz, Austria. barbara.obermayer@uni-graz.at
Lange
Uwe
U
Tauber
Gerlinde
G
Frühauf
Gerwig
G
Fahrleitner
Astrid
A
Dobnig
Harald
H
Hermann
Josef
J
Aglas
Ferdinand
F
Teichmann
Joachim
J
Neeck
Gunter
G
Leb
Georg
G
D015502:Absorptiometry, Photon / Q000379:methods; D000328:Adult; D001799:Blood Sedimentation; D015992:Body Mass Index; D015519:Bone Density / Q000502:physiology*; D002097:C-Reactive Protein / Q000032:analysis; D018387:Codon, Initiator / Q000235:genetics*; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D005838:Genotype; D015796:HLA-B27 Antigen / Q000032:analysis; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D010147:Pain Measurement; D011110:Polymorphism, Genetic / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012737:Sex Factors; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000503:physiopathology
D018387:Codon, Initiator; D015796:HLA-B27 Antigen; D018167:Receptors, Calcitriol; D002097:C-Reactive Protein