title: Association studies of calcium-sensing receptor (CaSR) polymorphisms with serum concentrations of glucose and phosphate, and vascular calcification in renal transplant recipients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Common CASR SNPs may be independent predictors of serum glucose and phosphate concentrations, but are not determinants of vascular calcification or cardiovascular outcomes.
authors.affiliation: Academic Endocrine Unit, Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Oxford, United Kingdom.
authors.forename: Valerie N
authors.initials: VN
authors.lastname: Babinsky
authors.affiliation: Academic Endocrine Unit, Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Oxford, United Kingdom.
authors.forename: Fadil M
authors.initials: FM
authors.lastname: Hannan
authors.affiliation: Institute of Physiology, Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
authors.forename: Sonia C
authors.initials: SC
authors.lastname: Youhanna
authors.affiliation: Division of Nephrology, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Maréchal
authors.affiliation: Division of Nephrology, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Jadoul
authors.affiliation: Institute of Physiology, Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; Division of Nephrology, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.affiliation: Academic Endocrine Unit, Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Oxford, United Kingdom.
authors.forename: Rajesh V
authors.initials: RV
authors.lastname: Thakker
mesh_terms: D001786:Blood Glucose / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000097:blood; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood*; D011401:Promoter Regions, Genetic; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D061205:Vascular Calcification / Q000235:genetics*
chemical_list: D001786:Blood Glucose; C095550:CASR protein, human; D010710:Phosphates; D044169:Receptors, Calcium-Sensing; D002118:Calcium