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

Abstract

Objective: The cytokine tumor necrosis factor alpha (TNF-a) is an important regulator of bone metabolism. Polymorphisms in the promoter region of the TNF-a gene at positions 2 308 and 2 863 have been identified. We investigated whether these polymorphisms and circulating TNF-a 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-a genotype. Methods: Allelic variants of the TNF-a 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 2863 A allele ðn ¼ 25Þ had higher body weight ðP ¼ 0:03Þ; lumbar spine BMD ðP ¼ 0:02Þ; and larger total BA ðP ¼ 0:03Þ; femoral neck area ðP , 0:05Þ; and lumbar spine area ðP ¼ 0:01Þ: The independent predictors of BMD and BA were investigated using multiple regression. The TNF-a 2 863 genotypes ðb ¼ 0:18; P ¼ 0:03Þ and the TNF-a plasma levels ðb ¼ 0:19; P ¼ 0:04Þ 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 2 308 ðP ¼ 0:17 -0:84Þ: Conclusions: We found the TNF-a 2 863 polymorphism and the TNF-a plasma levels to be independent predictors of lumbar spine area in healthy Caucasian adolescent females.

Effect of the TNFα-308 G/A Polymorphism on the Changes Produced by Atorvastatin in Bone Mineral Density in Patients with Acute Coronary Syndrome

“…Patients with the G/G genotype showed increased BMD in the lumbar spine in response to treatment while those with the G/A genotype did not. The genotype distribution of our patients was similar to the European distribution, with more than 70% having the G/G genotype, although different from Asia, where the AA genotype predominates [15,19,20] .…”

“…However, no significant association was found between the TNF ␣ -308 G/A polymorphism and the incidence of coronary disease [15] or osteoporosis (BMD) either in Europeans or Asians [19,20] . Nor does the polymorphism influence the peak bone mass although another polymorphism located in the promoter region of the gene, -863 CA [19] , does. Only Fontova et al [23] , in a study on 104 postmenopausal women with osteoporosis and 51 without, found a higher bone mass in a group of patients with nonsevere osteoporosis and the G allele.…”

Genetic Influence on Inflammation Variables in the Elderly

“…The fibrinogen ␤-455G/A promoter polymorphism was analyzed as described by Thomas et al 28 The CRP-1059G/C polymorphism was analyzed as described by Zee et al 29 The ICAM-1 K/E469 polymorphism was analyzed as described by Nishimura et al 30 The IL-6 -174C/T promoter polymorphism was analyzed as described by Fishman et al 24 The TNF-␣-238G/A promoter polymorphism was analyzed as described by Wennberg et al 31 The genotype was determined in all individuals and monozygosity was confirmed. In each PCR run, samples with known genotypes were included.…”

The Bone-Adipose Axis in Obesity and Weight Loss

“…It is overexpressed in adipose tissue, which is both a source of and a target for TNF-α [10,46]. TNF-α has been shown to stimulate bone resorption in vitro and in vivo being also implicated in diseases with increased osteoclastic bone resorption [53,54]. In addition, direct evidence of a stimulatory effect by TNF-α on osteoclastogenesis has been found in both human [55] and mouse [56] bone marrow cells.…”