Fontova R, Gutiérrez C, Vendrell J, Broch M, Vendrell I, Simón I, Fernández-Real J M, Richart C
University Hospital of Tarragona Joan XXIII, Medicine and Surgery Department, Spain.
J Endocrinol Invest. 2002 Sep;25(8):684-90. doi: 10.1007/BF03345101.
Bone mass is known to be under genetic control. Interleukin-1 (IL-1), interleukin-6 (IL-6) and TNF-alpha are strong inductors of bone resorption. The estrogenic deficiency that occurs during menopause leads to an increase in the production of these cytokines. We analyzed the genetic susceptibility of several polymorphisms of the interleukin-1 receptor antagonist (IL-1ra), IL-6 and TNF-alpha genes in lumbar spine and hip bone mass in a sample of post-menopausal Caucasian Mediterranean women with osteoporosis. 104 post-menopausal osteoporotic women (58.6+/-4.8 yr) and 51 post-menopausal women without osteoporosis as the control group (57.2+/-4.5 yr) were studied. The osteoporotic group was in turn sub-classified into severe and non-severe osteoporosis. The variable number of tandem repeats IL1-ra, IL-6 SfaNI and TNF-alpha NcoI genetic polymorphisms were studied. Biochemical markers of bone turnover were measured in blood and urine. Women carrying the A2 allele (A2+) of the IL-1ra gene showed greater BMD in the lumbar spine (p=0.02) and hip (p=0.006), compared to those not carrying the allele (A2-). The IL-6 polymorphism studied in its 5' flanking region did not show any association with BMD values. The TNF-alpha gene G allele was associated with a greater bone mass in the non-severe osteoporotic subgroup, both in the lumbar spine (p=0.0007) and in the hip (p=0.02). Likewise, genotype combination A2+GG was associated to a greater hip BMD at the femoral neck and Ward triangle levels (p=0.02). We conclude that both IL-1ra and TNF-alpha can be candidate loci to be studied in the susceptibility to develop post-menopausal osteoporosis.
已知骨量受基因控制。白细胞介素 -1（IL -1）、白细胞介素 -6（IL -6）和肿瘤坏死因子 -α（TNF -α）是骨吸收的强效诱导剂。绝经期间出现的雌激素缺乏会导致这些细胞因子的产生增加。我们分析了绝经后患有骨质疏松症的高加索地中海女性样本中白细胞介素 -1受体拮抗剂（IL -1ra）、IL -6和TNF -α基因的几种多态性对腰椎和髋部骨量的遗传易感性。研究了104名绝经后骨质疏松女性（58.6±4.8岁）和51名无骨质疏松的绝经后女性作为对照组（57.2±4.5岁）。骨质疏松组又分为重度和非重度骨质疏松。研究了IL1 - ra、IL -6 SfaNI和TNF -α NcoI基因多态性的串联重复可变数目。测量了血液和尿液中的骨转换生化标志物。与未携带该等位基因（A2 -）的女性相比，携带IL -1ra基因A2等位基因（A2 +）的女性在腰椎（p = 0.02）和髋部（p = 0.006）显示出更高的骨密度。在其5'侧翼区域研究IL -6多态性与骨密度值无任何关联。TNF -α基因G等位基因与非重度骨质疏松亚组中更高的骨量相关，在腰椎（p = 0.0007）和髋部（p = 0.02）均如此。同样，基因型组合A2 + GG与股骨颈和沃德三角水平更高的髋部骨密度相关（p = 0.02）。我们得出结论，IL -1ra和TNF -α都可能是研究绝经后骨质疏松症易感性的候选基因座。
