title: The genetic background of uremic secondary hyperparathyroidism.
abstract: Many studies have shown how gene mutations and genetic polymorphisms could influence secondary uremic hyperparathyroidism (HPTH), modulating parathyroid (PT) function and hyperplasia. Parathyroid hormone (PTH) gene expression and hormone secretion is regulated mainly by serum calcium, with a post-transcriptional effect, and by vitamin D with a transcriptional effect. PT cells retain the ability to proliferate and to apoptose. Hyperphosphatemia, hypocalcemia and vitamin D deficiency all stimulate PT cell proliferation. In the early stage of chronic uremia, PT proliferation is polyclonal, as in diffuse hyperplasia, whereas nodular hyperplasia growth is monoclonal with an increasingly recognized genetic background. HPTH has been associated with a number of familial diseases, such as multiple endocrine neoplasia-type 1 (MEN1), multiple endocrine neoplasia-type2A (MEN2A), neurofibromatosis type1 (NF1) and HPTH with multiple ossifying jaw fibromas (HPT-JT Syndrome). The genes involved in these diseases have been also investigated in secondary HPTH (sHPTH). Moreover, in sporadic and secondary uremic HPTH, clonal rearrangement and/or oncogene overexpression, gene deletions and tumor suppressor gene inactivation have been reported. However, each condition shows different patterns of genetic abnormalities. Finally, PT function modulation by genetic polymorphisms of vitamin D and calcium receptors and of the PTH gene is reviewed.
authors.affiliation: Department of Nephrology and Dialysis, Casa Sollievo della Sofferenza Hospital IRCCS, San Giovanni Rotondo--Italy. faucel@tin.it
authors.forename: Filippo
authors.initials: F
authors.lastname: Aucella
authors.forename: Luigi
authors.initials: L
authors.lastname: Morrone
authors.forename: Carmine
authors.initials: C
authors.lastname: Stallone
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
mesh_terms: D049109:Cell Proliferation; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000235:genetics* / Q000628:therapy; D007676:Kidney Failure, Chronic / Q000235:genetics; D009154:Mutation; D010280:Parathyroid Glands / Q000166:cytology; D010281:Parathyroid Hormone / Q000096:biosynthesis* / Q000378:metabolism; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics; D014511:Uremia / Q000235:genetics*
chemical_list: D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing