A novel polymorphism at the GNAS1 gene associated with low circulating calcium levels

Masi, Laura and Del Monte, Francesca and Gozzini, Alessia and De Feo, Maria Laura and Gionata Gheri, Riccardo and Neri, Annasilvia and Falchetti, Alberto and Amedei, Antonietta and Imbriaco, Rosario and Mavilia, Carmelo and Tanini, Annalisa and Brandi, Maria Luisa (2007) A novel polymorphism at the GNAS1 gene associated with low circulating calcium levels. Clinical cases in mineral and bone metabolism, 4 (2). pp. 139-145. ISSN 1971-3266

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Abstract

The concentration of calcium in the extracellular fluid is crucialfor several physiological functions in humans and in normalconditions its circulating levels are maintained between 8.5-10.5mg/dl. Among the regulators of calcium homeostasis parathyroid hormone (PTH) acts though the G-protein coupled PTH receptorand a hormone-sensitive adenylate cyclase, with Gs?subunit (stimulatory guanine nucleotide-binding protein alphasubunit) being responsible for the stimulation of the catalytic complex. Mutations of the Gs? encoding gene, GNAS1, are causal for some forms of congenital hypocalcemia. In the present study genetic variability in the GNAS1 gene was analyzed in a group of hypocalcemic patients collected through the Italian Register of Primary Hypoparathyroidism (RIIP). We identified a new intronic variant of the GNAS1 gene, consisting of a T>C polymorphism. This polymorphism was studied in a group of unrelated healthy subjects for a possible association with bone turnover biomarkers and bone mineral density. The T>C polymorphism was found in 18% of the studied populations, with 15% heterozygous TC and 3% homozygous CC (Pearson ?2 analysis: p=0.04). A significant association with low serum calcium levels was found in healthy subjects carrying the T > C polymorphism (ANCOVA analysis: p=0.04). These results support segregation of a novel GNAS1 gene intronic variant with low calcium levels in primary hypoparathyroidism, pseudo-hypoparathyroidism and in the general population.

Item Type:	Article
Uncontrolled Keywords:	Hypocalcemia; GS? Unit; GNAS1 gene; primary hypoparathyroidism; pseudo-hypoparathyroidism
Subjects:	600 Tecnologia - Scienze applicate > 610 Medicina e salute (Classificare qui la tecnologia dei servizi medici) > 612 Fisiologia umana > 612.7 Sistema muscoloscheletrico, tegumento
Depositing User:	Danilo Dezzi
Date Deposited:	20 Jan 2014 09:23
Last Modified:	20 Jan 2014 09:23
URI:	http://eprints.bice.rm.cnr.it/id/eprint/4944

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