In vitro characterization of a human calcitonin receptor gene polymorphism
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, ISSN: 0027-5107, Vol: 522, Issue: 1, Page: 93-105
2003
- 22Citations
- 6Captures
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Metrics Details
- Citations22
- Citation Indexes22
- 22
- CrossRef16
- Captures6
- Readers6
Article Description
Calcitonin is a 32 amino acid peptide hormone that inhibits bone resorption by stimulating calcitonin receptors (CTR) located on the surfaces of osteoclasts. A polymorphism at nucleotide 1340 of the human calcitonin receptor gene (CALCR) lies within the coding region and has the potential to change the amino acid at codon 447 from leucine to proline. In the present study, we scanned the coding region, portions of the 5′-flanking and 3′-flanking sequences, and the intron–exon boundaries of the human CALCR gene for additional polymorphisms, and determined the frequency of the codon 447 polymorphism in several ethnic groups. Because a leucine to proline change has the potential for significant structural alteration, receptor genes encoding either leucine or proline at residue 447 were transiently expressed in COS-7 cells to determine the binding and functional consequences of this polymorphism. Our complete polymorphism scan of the CALCR gene identified 11 polymorphic sites in the gene and confirmed the presence of the previously identified nucleotide T1340C (codon 447) polymorphism. Ten of the 11 polymorphisms were single nucleotide polymorphisms (SNPs). For the codon 447 polymorphism, the prevalence of the TT genotype (leucine) was 59% in Caucasians, 27% in African–Americans, 0% in Asians, and 20% in Hispanics. The presence of this SNP appears to have no statistically significant difference with the receptor’s ability to bind calcitonin or signal when activated with the hormone.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0027510702002828; http://dx.doi.org/10.1016/s0027-5107(02)00282-8; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0037469394&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/12517415; http://linkinghub.elsevier.com/retrieve/pii/S0027510702002828; http://api.elsevier.com/content/article/PII:S0027510702002828?httpAccept=text/xml; http://api.elsevier.com/content/article/PII:S0027510702002828?httpAccept=text/plain; https://linkinghub.elsevier.com/retrieve/pii/S0027510702002828; http://dx.doi.org/10.1016/s0027-5107%2802%2900282-8; https://dx.doi.org/10.1016/s0027-5107%2802%2900282-8
Elsevier BV
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