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OBJECTIVE: The cytokine tumor necrosis factor alpha (TNF-alpha) is an important regulator of bone metabolism. Polymorphisms in the promoter region of the TNF-alpha gene at positions -308 and -863 have been identified. We investigated whether these polymorphisms and circulating TNF-alpha levels were related to bone mineral density and bone area in adolescent girls. DESIGN: Bone mineral density (BMD), bone area (BA), anthropometric characteristics and biochemical analyses were measured in adolescent girls and compared with regard to TNF-alpha genotype. METHODS: Allelic variants of the TNF-alpha gene in 97 girls, aged 16.9+/-1.2 years (mean+/-S.D.), were identified using polymerase chain reaction and the restriction endonucleases NcoI and TaiI. Bone mineral density and bone area of the femoral neck, lumbar spine and total body were measured using dual energy X-ray absorptiometry. RESULTS: Carriers of the rare -863 A allele (n=25) had higher body weight (P=0.03), lumbar spine BMD (P=0.02), and larger total BA (P=0.03), femoral neck area (P&lt;0.05), and lumbar spine area (P=0.01). The independent predictors of BMD and BA were investigated using multiple regression. The TNF-alpha-863 genotypes (beta=0.18, P=0.03) and the TNF-alpha plasma levels (beta=0.19, P=0.04) independently predicted BA of the lumbar spine but not BA or BMD of any other measured sites. No statistically significant differences in body constitution parameters, biochemical parameters, bone density, or bone area at the measured skeletal sites were found when comparing the groups defined by the allelic variants at position -308 (P=0.17-0.84). CONCLUSIONS: We found the TNF-alpha-863 polymorphism and the TNF-alpha plasma levels to be independent predictors of lumbar spine area in healthy Caucasian adolescent females.

TNF-alpha gene polymorphism and plasma TNF-alpha levels are related to lumbar spine bone area in healthy female Caucasian adolescents