Analysis of Somatostatin Receptors 2 and 5 Polymorphisms in Patients with Acromegaly

Journal of Clinical Endocrinology and Metabolism - Tập 90 Số 8 - Trang 4824-4828 - 2005
Marcello Filopanti1, Cristina L. Ronchi1, Emilia Ballarè1, Sara Bondioni1, Andrea Lania1, Marco Losa2, Stefania Gelmini3, Alessandro Peri4, Claudio Orlando3, P. Beck‐Peccoz1, Anna Spada1
1Institute of Endocrine Sciences (M.F., C.R., E.B., S.B., A.G.L., P.B.-P., A.S.), University of Milan, Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Istituto di Ricovero e Cura a Curattere Scientifico, 20122 Milan, Italy
2Pituitary Unit (M.L.), Department of Neurosurgery, Ospedale San Raffaele, Istituto di Ricovero e Cura a Curattere Scientifico, 20132 Milan, Italy
3Clinical Biochemistry (S.G., C.O.), 50121 Florence, Italy
4Endocrine Units (A.P.), Department of Clinical Physiopathology, University of Florence, 50121 Florence, Italy

Tóm tắt

Objective: The aim of the study was to investigate the possible correlation of single nucleotide polymorphisms in somatostatin receptor (SSTR)2 and SSTR5 genes with the responsiveness to somatostatin analogs in a cohort of acromegalic patients. Study Design: Three single nucleotide polymorphisms (a-83 g, c-57 g, and t80c) of SSTR2 and three (t-461c, c325t, and c1004t) of SSTR5 were analyzed in 66 acromegalic patients with different responsiveness to somatostatin analogs and 66 healthy controls. Results: Allele frequencies in patients and controls were similar. No association between SSTR2 genotypes and GH and IGF-I levels was found. When considering SSTR5 variants, patients homozygous or heterozygous for the substitution c1004 (P+) showed basal IGF-I levels significantly lower than patients homozygous for 1004t (P−). Moreover, serum GH levels were lower in patients with P+/T− haplotype (having c1004 allele and no t-461 allele) than in those with P−/T+. No correlation between SSTR2 and SSTR5 genotypes, responsiveness to somatostatin therapy, and mRNA expression in the removed adenomas (n = 10) was found. Conclusions: These data suggest a role for SSTR5 t–461c and c1004t alleles in influencing GH and IGF-I levels in patients with acromegaly, whereas SSTR2 and SSTR5 variants seem to have a minor role in determining the responsiveness to somatostatin analogs.

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Tài liệu tham khảo

Greenman, 1994, Heterogenous expression of two somatostatin receptor subtypes in pituitary tumors., J Clin Endocrinol Metab, 78, 398

Miller, 1995, Somatostatin receptor subtype gene expression in pituitary adenomas., J Clin Endocrinol Metab, 80, 1386

Panetta, 1995, Expression of mRNA for all five human somatostatin receptors (hSSTR1–5) in pituitary tumors., Life Sci, 56, 333, 10.1016/0024-3205(94)00956-2

Lamberts, 1991, The role of somatostatin and its analogs in the diagnosis and treatment of tumors., Endocr Rev, 12, 450, 10.1210/edrv-12-4-450

Yamada, 1992, Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract and kidney., Proc Natl Acad Sci USA, 89, 251, 10.1073/pnas.89.1.251

Raynor, 1993, Cloned somatostatin receptors: identification of subtype-selective peptides and demonstration of high affinity of linear peptides., Mol Pharmacol, 43, 838

Barlier, 1999, Impact of gsp oncogene on the expression of genes coding for Gsα, Pit-1, Gi2α, and somatostatin receptor 2 in human somatotroph adenomas: involvement in octreotide sensitivity., J Clin Endocrinol Metab, 84, 2759

Jaquet, 2000, Human somatostatin receptor subtypes in acromegaly: distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes., J Clin Endocrinol Metab, 85, 781

Petersen, 2000, Absence of somatostatin receptor type 2A mutations and gip oncogene in pituitary somatotroph adenomas., Clin Endocrinol (Oxf), 52, 35, 10.1046/j.1365-2265.2000.00880.x

Corbetta, 2001, Somatostatin receptor subtype 2 and 5 in human GH-secreting pituitary adenomas: analysis of gene sequence and mRNA expression., Eur J Clin Invest, 31, 208, 10.1046/j.1365-2362.2001.00786.x

Ballarè, 2001, Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treatment., J Clin Endocrinol Metab, 86, 3809, 10.1210/jcem.86.8.7787

Nyegaard, 2002, Novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene associated with bipolar affective disorder., Mol Psychiatry, 7, 745, 10.1038/sj.mp.4001049

Torrisani, 2001, Transcription of SST2 somatostatin receptor gene in human pancreatic cancer cells is altered by single nucleotide promoter polymorphism., Gastroenterology, 120, 200, 10.1053/gast.2001.21192

Orlando, 1998, Developments in quantitative PCR., Clin Chem Lab Med, 36, 255, 10.1515/CCLM.1998.045

Casini Raggi, 2002, Quantitative evaluation of somatostatin receptor subtype 2 expression in sporadic colorectal tumor and in the corresponding normal mucosa., Clin Cancer Res, 8, 419

Saveanu, 2001, Bim-23244, a somatostatin receptor subtype 2- and 5-selective analog with enhanced efficacy in suppressing growth hormone (GH) from octreotide-resistant human GH-secreting adenomas., J Clin Endocrinol Metab, 86, 140

Hofland, 2004, Somatostatin receptors in pituitary function, diagnosis and therapy., Front Horm Res, 32, 235, 10.1159/000079048

Sharma, 1999, C-terminal region of the human somatostatin receptor 5 is required for induction of Rb and G1 cell cycle arrest., Mol Endocrinol, 13, 82, 10.1210/mend.13.1.0220

Rocheville, 2000, Receptor for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity., Science, 288, 154, 10.1126/science.288.5463.154

Arosio, 2003, Elevated circulating somatostatin levels in acromegaly., J Endocrinol Invest, 26, 499, 10.1007/BF03345210

Hurley, 1994, Increased hypothalamic somatostatin expression in mice transgenic for bovine or human GH., J Neuroendocrinol, 6, 539, 10.1111/j.1365-2826.1994.tb00617.x

Filopanti, 2004, Loss of heterozygosity at the somatostatin receptor type 5 locus in human GH- and TSH-secreting pituitary adenomas., J Endocrinol Invest, 27, 937, 10.1007/BF03347536

Rietveld, 2003, A polymorphism in the IGF-I gene influences the age-related decline in circulating total IGF-I levels, Eur J Endocrinol 148, 171, 10.1530/eje.0.1480171

Amendt, 1999, Transcriptional antagonism between Hmx1 and Nkx2.5 for a shared DNA-binding site., J Biol Chem, 274, 11635, 10.1074/jbc.274.17.11635

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Thông tin xuất bản

Journal of Clinical Endocrinology and Metabolism

Tập 90 Số 8

4824-4828

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