Polymorphisms in the interleukin-6 receptor gene are associated with bone mineral density and body mass index in Spanish postmenopausal women
Polymorphisms in the interleukin-6 receptor gene are associated with bone mineral density and body mass index in Spanish postmenopausal women
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DOI：
10.1530/eje-07-0389
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发表时间：
2007-11-01
影响因子：
5.8
通讯作者：
Balcells, S.
中科院分区：
文献类型：
--
作者：
Bustamante, M.;Nogues, X.;Balcells, S.
目的：骨质疏松症和肥胖是复杂的疾病，具有很强的遗传成分。骨密度(BMD)和体重指数(BMI)连锁研究发现，白介素6受体(IL6R)基因位于1q21-23。IL6R和GP130受体是IL6作用的中介。在骨质疏松或肥胖等疾病中，血清IL6和sIL6R(IL6R的可溶性形式)水平较高。IL6R基因的变异与BMI和肥胖有关。设计：在本研究中，我们分析了IL6R启动子-1435C/T(Rs3887104)和-208G/A(Rs4845617)以及Asp358Ala多态(Rs8192284)与骨密度和体重指数的关系。结果：启动子-1435C/T和-208G/A与股骨颈骨密度相关(分别为P=0.011和P=0.025)。C-A和T-G启动子单倍型也与FN骨密度相关。此外，AsP3 5 8Ala变异与腰椎骨密度相关(P=0.0 3 8)。-208G/A多态、C-G和C-A单倍型与体重指数和肥胖相关，其中GG是肥胖的危险基因(P=0.033，P=0.010)。结论：IL-6R基因变异不仅参与了体重指数的测定，而且与骨密度的测定有关。IL6R基因可能属于越来越多的已知与这两种表型有关的基因。
Objective: Osteoporosis and obesity are complex diseases with a strong genetic component. Bone mineral density (BMD) and body mass index (BMI) linkage studies identified a locus at 1q21-23, where the interleukin-6 receptor (IL6R) gene is located. The IL6R and the gp1 30 receptors are the mediators of IL6 action. Serum levels of IL6 and sIL6R (the soluble form of IL6R) are higher in several diseases such as osteoporosis or obesity. Variants at IL6R have been associated with BMI and obesity. However, IL6R is an as-yet-unexplored osteoporosis candidate gene.Design: In the present study we analysed two polymorphisms in the IL6R promoter, - 143 5 C/T (rs3887104) and -208 G/A (rs4845617), and the Asp358Ala polymorphism (rs8192284), in relation to both BMD and BMI in a cohort of 559 postmenopausal Spanish women.Results: The promoter polymorphisms, - 143 5 C/T and - 208 G/A were associated with femoral neck (FN) BMD (P=0.011 and P=0.025 respectively). The C-A and T-G promoter haplotypes were also associated with FN BMD. Additionally, the Asp3 5 8Ala variant was associated with lumbar spine BMD (P = 0.03 8). Finally, the - 208 G/A polymorphism and the C-G and C-A haplotypes were associated with BMI and obesity, where GG was the risk genotype (P=0.033 for BMI; P=0.010 for obesity).Conclusion: These data suggest that variants in the IL6R gene are not only involved in the determination of BMI but also relevant for the determination of BMD. The IL6R gene may belong to the growing list of genes known to be involved in both phenotypes.