PMID- 10023897
OWN - NLM
STAT- MEDLINE
DCOM- 19990304
LR  - 20190611
IS  - 0140-6736 (Print)
IS  - 0140-6736 (Linking)
VI  - 353
IP  - 9147
DP  - 1999 Jan 9
TI  - A986S polymorphism of the calcium-sensing receptor and circulating calcium
      concentrations.
PG  - 112-5
AB  - BACKGROUND: The regulation of extracellular calcium concentration by parathyroid 
      hormone is mediated by a calcium-sensing, G-protein-coupled cell-surface receptor
      (CASR). Mutations of the CASR gene alter the set-point for extracellular ionised 
      calcium [Ca2+]o and cause familial hypercalcaemia or hypocalcaemia. The CASR
      missense polymorphism, A986S, is common in the general population and is,
      therefore, a prime candidate as a genetic determinant of extracellular calcium
      concentration. METHODS: We genotyped the CASR A986S variant (S allele frequency
      of 16.3%) in 163 healthy adult women and tested samples of their serum for total 
      calcium, albumin, total protein, creatinine, phosphate, pH, and parathyroid
      hormone. A prospectively generated, random subset of 84 of these women provided a
      whole blood sample for assay of [Ca2+]o. FINDINGS: The A986S genotype showed no
      association with total serum concentration of calcium, until corrected for
      albumin. In a multivariate regression model, biochemical and genetic variables
      accounted for 74% of the total variation in calcium. The significant predictors
      of serum calcium were: albumin (p<0.001), phosphate (p=0.02), parathyroid hormone
      (p=0.007), pH (p=0.001), and A986S genotype (p=0.009). Fasting whole-blood
      [Ca2+]o also showed an independent positive association with the 986S variant
      (p=0.013). INTERPRETATION: The CASR A986S variant has a significant effect on
      extracellular calcium. The CASR A986S polymorphism is a likely candidate locus
      for genetic predisposition to various bone and mineral disorders in which
      extracellular calcium concentrations have a prominent part.
FAU - Cole, D E
AU  - Cole DE
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto,
      Ontario, Canada. davidec.cole@utoronto.ca
FAU - Peltekova, V D
AU  - Peltekova VD
FAU - Rubin, L A
AU  - Rubin LA
FAU - Hawker, G A
AU  - Hawker GA
FAU - Vieth, R
AU  - Vieth R
FAU - Liew, C C
AU  - Liew CC
FAU - Hwang, D M
AU  - Hwang DM
FAU - Evrovski, J
AU  - Evrovski J
FAU - Hendy, G N
AU  - Hendy GN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Lancet
JT  - Lancet (London, England)
JID - 2985213R
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (Receptors, Cell Surface)
RN  - SY7Q814VUP (Calcium)
SB  - IM
CIN - Lancet. 1999 Jan 9;353(9147):83-4. PMID: 10023887
CIN - Lancet. 1999 Apr 10;353(9160):1274. PMID: 10217111
MH  - Adolescent
MH  - Adult
MH  - Calcium/*blood
MH  - Female
MH  - Genetic Predisposition to Disease/genetics
MH  - Genetic Variation
MH  - Genotype
MH  - Humans
MH  - Hypercalcemia/blood/genetics
MH  - Hypocalcemia/blood/genetics
MH  - Linkage Disequilibrium/genetics
MH  - Polymorphism, Genetic/*genetics
MH  - Prospective Studies
MH  - Receptors, Calcium-Sensing
MH  - Receptors, Cell Surface/*genetics
EDAT- 1999/02/19 00:00
MHDA- 1999/02/19 00:01
CRDT- 1999/02/19 00:00
PHST- 1999/02/19 00:00 [pubmed]
PHST- 1999/02/19 00:01 [medline]
PHST- 1999/02/19 00:00 [entrez]
AID - S0140673698064344 [pii]
AID - 10.1016/s0140-6736(98)06434-4 [doi]
PST - ppublish
SO  - Lancet. 1999 Jan 9;353(9147):112-5. doi: 10.1016/s0140-6736(98)06434-4.