Genetic variation at the calcium-sensing receptor (CASR) locus: implications for clinical molecular diagnostics

Clin Biochem. 2007 May;40(8):551-61. doi: 10.1016/j.clinbiochem.2006.12.011. Epub 2007 Jan 18.


Objectives: The calcium-sensing receptor (CASR) is critical for maintenance of blood calcium in a narrow physiologic range. Naturally occurring mutations in the calcium-sensing receptor gene (CASR) cause hypocalcaemia or hypercalcaemia, and molecular diagnosis of these mutations is clinically important. Knowledge of SNP frequency and haplotype structure is essential in understanding molecular test results.

Design and methods: Genotyping and haplotype analysis of 26 CASR SNPs (and a tetranucleotide insertion/deletion polymorphism) in control cohorts of Caucasian, Asian and African-American origin (n=1136, 88 and 104 chromosomes, respectively).

Results: The three SNPs in exon 7 (A986S, R990G, Q1011E) are the only common exonic variants in our cohorts, and synonymous exonic SNPs are uncommon. Linkage disequilibrium analysis of the Caucasian cohort (Haploview) showed that the CASR locus is divided into three haplotype blocks, coincident with 5' regulatory, coding, and 3' regulatory domains.

Conclusions: These analyses provide an important framework for appropriate interpretation of CASR mutation screening now offered by a number of laboratories for the diagnosis of calcium disorders. They will assist in the study of CASR polymorphisms as predictors of complex disease states.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans / genetics
  • Alleles
  • Asians / genetics
  • Base Sequence
  • Cohort Studies
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genotype
  • Haplotypes
  • Humans
  • Hypercalcemia / diagnosis
  • Hypercalcemia / genetics
  • Hypocalcemia / diagnosis
  • Hypocalcemia / genetics
  • Linkage Disequilibrium
  • Models, Genetic
  • Mutation*
  • Polymorphism, Single Nucleotide
  • Receptors, Calcium-Sensing / genetics*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Whites / genetics


  • Receptors, Calcium-Sensing