Lorentzon M, Lorentzon R, Nordström P
Department of Surgical and Perioperative Sciences, Umeå University, Sweden.
J Bone Miner Res. 2000 Oct;15(10):1944-9. doi: 10.1359/jbmr.2000.15.10.1944.
Bone mineral density (BMD) is under strong genetic control and is the major determinant of fracture risk. The cytokine interleukin-6 (IL-6) is an important regulator of bone metabolism and is involved in mediating the effects of androgens and estrogens on bone. Recently, a G/C polymorphism in position -174 of the IL-6 gene promoter was found. We investigated this genetic polymorphism in relation to BMD during late puberty and to peak bone mass, in healthy white males. We identified the IL-6 genotypes (GG, GC, and CC) in 90 boys, age 16.9 +/- 0.3 years (mean +/- SD), using polymerase chain reaction (PCR). BMD (g/cm2) at the femoral neck, lumbar spine, and total body was measured using dual energy X-ray absorptiometry. The volumetric BMD (vBMD; mg/cm3) of the lumbar spine was estimated. Differences in BMD in relation to the genotypes were calculated using analysis of variance (ANOVA). Subjects with the CC genotype had 7.9% higher BMD of the femoral neck (p = 0.03), 7.0% higher BMD of the lumbar spine (p < 0.05), and 7.6% higher vBMD of the lumbar spine (p = 0.04), compared with their GG counterparts. Using multiple regression, the IL-6 genotypes were independently related to total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p < 0.05), neck BMD (CC > GG; p = 0.01), spine BMD (CC > GG; p = 0.01), and spine vBMD (CC > GG; p = 0.008). At age 19.3 +/- 0.7 years (mean +/- SD; 88 men) the IL-6 genotypes were still independent predictors for total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p = 0.03), spine BMD (CC > GG; p = 0.02), and spine vBMD (CC > GG; p = 0.003), while the IL-6 genotypes were not related to the increase in bone density seen after 2 years. We have shown that polymorphism of the IL-6 gene is an independent predictor of BMD during late puberty and of peak bone mass in healthy white men.
骨矿物质密度（BMD）受强大的基因控制，是骨折风险的主要决定因素。细胞因子白细胞介素-6（IL-6）是骨代谢的重要调节因子，参与介导雄激素和雌激素对骨骼的作用。最近，在IL-6基因启动子的-174位发现了一个G/C多态性。我们在健康的白人男性中研究了这种基因多态性与青春期后期骨矿物质密度以及峰值骨量的关系。我们使用聚合酶链反应（PCR）对90名年龄为16.9±0.3岁（平均±标准差）的男孩进行了IL-6基因型（GG、GC和CC）鉴定。使用双能X线吸收法测量股骨颈、腰椎和全身的骨矿物质密度（g/cm²）。估算腰椎的体积骨矿物质密度（vBMD；mg/cm³）。使用方差分析（ANOVA）计算与基因型相关的骨矿物质密度差异。与GG基因型的受试者相比，CC基因型的受试者股骨颈骨矿物质密度高7.9%（p = 0.03），腰椎骨矿物质密度高7.0%（p < 0.05），腰椎体积骨矿物质密度高7.6%（p = 0.04）。通过多元回归分析，IL-6基因型与全身骨矿物质密度（CC > GG；p = 0.03）、肱骨骨矿物质密度（CC > GG；p < 0.05）、颈部骨矿物质密度（CC > GG；p = 0.01）、脊柱骨矿物质密度（CC > GG；p = 0.01）和脊柱体积骨矿物质密度（CC > GG；p = 0.008）独立相关。在19.3±0.7岁（平均±标准差；88名男性）时，IL-6基因型仍然是全身骨矿物质密度（CC > GG；p = 0.03）、肱骨骨矿物质密度（CC > GG；p = 0.03）、脊柱骨矿物质密度（CC > GG；p = 0.02）和脊柱体积骨矿物质密度（CC > GG；p = 0.003）的独立预测因子，而IL-6基因型与2年后观察到的骨密度增加无关。我们已经表明，IL-6基因多态性是健康白人男性青春期后期骨矿物质密度和峰值骨量的独立预测因子。
