Di Nisio Andrea, Rocca Maria Santa, Fadini Gian Paolo, De Toni Luca, Marcuzzo Giorgio, Marescotti Maria Cristina, Sanna Marta, Plebani Mario, Vettor Roberto, Avogaro Angelo, Foresta Carlo
Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
Division of Metabolic Diseases, Department of Medicine, University of Padova, Padova, Italy.
Clin Endocrinol (Oxf). 2017 Feb;86(2):185-191. doi: 10.1111/cen.13248. Epub 2016 Oct 21.
Identification of the novel endocrine role of osteocalcin (OC) and its receptor GPRC6A has given rise to a new branch of research in OC/GPRC6A axis related to glucose metabolism. GPRC6A- and OC-deficient mice share features of the metabolic syndrome, in addition to male infertility. Recently, the polymorphism rs2274911 in GPRC6A was shown to be associated with testicular impairment. We aimed to investigate the role of rs2274911 polymorphism in glucose and lipid metabolism in a cohort of normal weight and obese subjects DESIGN, PATIENTS, SETTINGS: A total of 392 male and females, including 218 obese patients and 174 age-matched normal weight controls, were retrospectively selected.
The distribution of rs2274911 alleles and genotypes did not differ either between normal weight and obese subjects or sexes (all P > 0·05). Age- and OC-adjusted multivariate analysis revealed that, in the normal weight group, fasting insulin and HOMA-IR increased in GA (P = 0·016 and P = 0·025) and AA genotypes (P = 0·033 and P = 0·040) compared with GG homozygotes. In the obese group, AA homozygotes had increased fasting glucose (P = 0·041 vs GG). Triglycerides, fasting insulin and HOMA-IR increased in both GA (P = 0·020, P < 0·001 and P = 0·001) and AA genotype (P = 0·021, P = 0·013 and P = 0·013).
In a cohort of normal weight and obese subjects, we found that the nonrare polymorphism rs2274911 in the GPRC6A gene was associated with insulin resistance features, independently of the metabolic phenotype and OC levels.
骨钙素（OC）及其受体GPRC6A新的内分泌作用的发现，催生了OC/GPRC6A轴中与葡萄糖代谢相关的一个新的研究分支。除了雄性不育外，GPRC6A和OC缺陷小鼠还具有代谢综合征的特征。最近，GPRC6A中的rs2274911多态性被证明与睾丸损伤有关。我们旨在研究rs2274911多态性在一组正常体重和肥胖受试者的葡萄糖和脂质代谢中的作用。设计、患者、研究背景：回顾性选取了392名男性和女性，包括218名肥胖患者和174名年龄匹配的正常体重对照者。
rs2274911等位基因和基因型的分布在正常体重和肥胖受试者之间或性别之间均无差异（所有P>0.05）。年龄和OC校正的多变量分析显示，在正常体重组中，与GG纯合子相比，GA（P = 0.016和P = 0.025）和AA基因型（P = 0.033和P = 0.040）的空腹胰岛素和HOMA-IR升高。在肥胖组中，AA纯合子的空腹血糖升高（与GG相比，P = 0.041）。GA（P = 0.020，P<0.001和P = 0.001）和AA基因型（P = 0.021，P = 0.013和P = 0.013）的甘油三酯、空腹胰岛素和HOMA-IR均升高。
在一组正常体重和肥胖受试者中，我们发现GPRC6A基因中不罕见的rs2274911多态性与胰岛素抵抗特征相关，独立于代谢表型和OC水平。
