Babinsky Valerie N, Hannan Fadil M, Youhanna Sonia C, Maréchal Céline, Jadoul Michel, Devuyst Olivier, Thakker Rajesh V
Academic Endocrine Unit, Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Oxford, United Kingdom.
Institute of Physiology, Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
PLoS One. 2015 Mar 18;10(3):e0119459. doi: 10.1371/journal.pone.0119459. eCollection 2015.
Cardiovascular disease is the major cause of death in renal transplant recipients (RTRs) and linked to arterial calcification. The calcium-sensing receptor (CaSR), a G-protein coupled receptor, plays a pivotal role in extracellular calcium homeostasis and is expressed in the intimal and medial layers of the arterial wall. We investigated whether common CASR gene variants are predictors for aortic and coronary artery calcification or influence risk factors such as serum calcium, phosphate and glucose concentrations in RTRs.
Two hundred and eighty four RTRs were investigated for associations between three CASR promoter region single nucleotide polymorphisms (SNPs) (rs115759455, rs7652589, rs1501899), three non-synonymous CASR coding region SNPs (A986S, R990G, Q1011E), and aortic and coronary artery calcium mass scores, cardiovascular outcomes and calcification risk factors that included serum phosphate, calcium, total cholesterol and glucose concentrations.
Multivariate analysis revealed that RTRs homozygous for the minor allele (SS) of the A986S SNP, when compared to those homozygous for the major allele (AA), had raised serum glucose concentrations (8.7±5.4 vs. 5.7±2.1 mmol/L, P<0.05). In addition, RTRs who were heterozygous (CT) at the rs115759455 SNP, when compared to those homozygous for the major allele (CC), had higher serum phosphate concentrations (1.1±0.3 vs. 1.0±0.2 mmol/L, P<0.05). CASR SNPs were not significant determinants for aortic or coronary artery calcification, and were not associated with cardiovascular outcomes or mortality in this RTR cohort.
Common CASR SNPs may be independent predictors of serum glucose and phosphate concentrations, but are not determinants of vascular calcification or cardiovascular outcomes.
心血管疾病是肾移植受者（RTR）死亡的主要原因，且与动脉钙化有关。钙敏感受体（CaSR）是一种G蛋白偶联受体，在细胞外钙稳态中起关键作用，且在动脉壁的内膜和中膜层表达。我们研究了常见的CaSR基因变异是否为主动脉和冠状动脉钙化的预测指标，或是否影响RTR的血清钙、磷和葡萄糖浓度等危险因素。
对284例RTR进行研究，分析三个CaSR启动子区域单核苷酸多态性（SNP）（rs115759455、rs7652589、rs1501899）、三个非同义CaSR编码区域SNP（A986S、R990G、Q1011E）与主动脉和冠状动脉钙质量评分、心血管结局以及钙化危险因素（包括血清磷、钙、总胆固醇和葡萄糖浓度）之间的关联。
多变量分析显示，与A986S SNP次要等位基因纯合子（SS）的RTR相比，主要等位基因纯合子（AA）的RTR血清葡萄糖浓度升高（8.7±5.4 vs. 5.7±2.1 mmol/L，P<0.05）。此外，与rs115759455 SNP杂合子（CT）的RTR相比，主要等位基因纯合子（CC）的RTR血清磷浓度更高（1.1±0.3 vs. 1.0±0.2 mmol/L，P<0.05）。CaSR SNP不是主动脉或冠状动脉钙化的显著决定因素，且与该RTR队列的心血管结局或死亡率无关。
常见的CaSR SNP可能是血清葡萄糖和磷浓度的独立预测指标，但不是血管钙化或心血管结局的决定因素。
