Effect of vitamin D receptor gene alleles on bone loss in early rheumatoid arthritis.
OBJECTIVE
Rheumatoid arthritis (RA) is a polygenic disease characterized by localized joint destruction and generalized osteoporosis resulting in increased fracture risk. The pathogenetic mechanisms that determine the severity of generalized bone loss in RA are poorly understood. Polymorphisms in the vitamin D receptor (VDR) gene have been described as a significant determinant of bone turnover and mass. In this prospective study we describe VDR gene allele effects on bone loss in patients with early RA.


METHODS
We recruited 232 patients with early RA. Bone mineral density measurements were repeated in 167 patients. Serial clinical and laboratory measures were recorded during the period of followup. DNA extraction, polymerase chain reaction amplification, and restriction fragment length polymorphism analysis of VDR alleles were performed using standard techniques. Presence of the Taq restriction site for both alleles was denoted "tt", and absence "TT".


RESULTS
In women with RA the tt genotype group lost bone more rapidly than subjects with TT genotype at both the lumbar spine (-0.1 vs -4.9% p.a, respectively; p < 0.05) and femoral neck (-3.9 vs -9.6%, respectively; p < 0.01). The effect was independent of other disease characteristics.


CONCLUSIONS
The presence of the VDR gene "t" allele in female patients with RA was associated with accelerated bone loss.
Gough
A
A
Rheumatology and Rehabilitation Research Unit, University of Leeds, UK.
Sambrook
P
P
Devlin
J
J
Lilley
J
J
Huisoon
A
A
Betteridge
J
J
Franklyn
J
J
Nguyen
T
T
Morrison
N
N
Eisman
J
J
Emery
P
P
D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000503:physiopathology; D015519:Bone Density / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics*
D005819:Genetic Markers; D006684:HLA-DR Antigens; D018167:Receptors, Calcitriol