Garg Gaurav, McGuigan Fiona E, Kumar Jitender, Luthman Holger, Lyssenko Valeriya, Akesson Kristina
Clinical and Molecular Osteoporosis Research Unit, Dept. of Clinical Science Malmö, Lund University; Dept of Orthopaedics, Skåne University Hospital Malmö, Sweden.
Dept of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Bone Rep. 2015 Dec 17;4:23-27. doi: 10.1016/j.bonr.2015.12.001. eCollection 2016 Jun.
The gastro-intestinal hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-induced insulin secretion, with bone anabolic effects through GIP receptor (GIPR) in animal models. We explore its potential in humans by analyzing association between polymorphisms (SNPs) in the and genes with bone phenotypes in young and elderly women.
Association between (rs2291725) and (rs10423928) and BMD, bone mineral content (BMC), bone microarchitecture, fracture and body composition was analyzed in the OPRA (75y, n = 1044) and PEAK-25 (25y; n = 1061) cohorts and serum-GIP in OPRA.
The receptor AA-genotype was associated with lower ultrasound values in young women (BUA p = 0.011; SI p = 0.030), with no association to bone phenotypes in the elderly. In the elderly, the was associated with lower ultrasound (GG vs. AA; SOS p = 0.021) and lower femoral neck BMD and BMC after adjusting for fat mass (p = 0.016 and p = 0.03). In young women, neither nor associated with other bone phenotypes including spine trabecular bone score. In the elderly, neither SNP associated with fracture. was associated with body composition only in Peak-25; was not associated with body composition in either cohort. Serum-GIP levels (in elderly) were not associated with bone phenotypes, however lower levels were associated with the A-allele (β = - 6.93; p = 0.03).
This first exploratory association study between polymorphisms in and in relation to bone phenotypes and serum-GIP in women at different ages indicates a possible, albeit complex link between glucose metabolism genes and bone, while recognizing that further studies are warranted.
胃肠激素葡萄糖依赖性促胰岛素多肽（GIP）可增强葡萄糖诱导的胰岛素分泌，在动物模型中通过GIP受体（GIPR）发挥骨合成代谢作用。我们通过分析年轻和老年女性中GIPR和GIP基因多态性（SNP）与骨表型之间的关联，来探索其在人类中的潜在作用。
在OPRA（75岁，n = 1044）和PEAK - 25（25岁；n = 1061）队列中分析GIPR（rs2291725）和GIP（rs10423928）与骨密度（BMD）、骨矿物质含量（BMC）、骨微结构、骨折和身体成分之间的关联，并在OPRA中分析血清GIP。
GIPR受体AA基因型与年轻女性较低的超声值相关（宽带超声衰减p = 0.011；超声积分p = 0.030），与老年女性的骨表型无关。在老年女性中，调整脂肪量后，GIP与较低的超声值（GG与AA比较；声速p = 0.021）以及较低的股骨颈BMD和BMC相关（p = 0.016和p = 0.03）。在年轻女性中，GIPR和GIP均与包括脊柱小梁骨评分在内的其他骨表型无关。在老年女性中，两个SNP均与骨折无关。GIP仅在PEAK - 25队列中与身体成分相关；在两个队列中GIPR均与身体成分无关。血清GIP水平（在老年女性中）与骨表型无关，然而较低水平与GIP的A等位基因相关（β = - 6.93；p = 0.03）。
这项关于不同年龄女性中GIPR和GIP基因多态性与骨表型及血清GIP之间的首次探索性关联研究表明，尽管关系复杂，但葡萄糖代谢基因与骨骼之间可能存在联系，同时认识到仍需进一步研究。
