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

Institute 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; Pituitary Unit (M.L.), Department of Neurosurgery, Ospedale San Raffaele, Istituto di Ricovero e Cura a Curattere Scientifico, 20132 Milan, Italy; and Clinical Biochemistry (S.G., C.O.) and Endocrine Units (A.P.), Department of Clinical Physiopathology, University of Florence, 50121 Florence, Italy

Address all correspondence and requests for reprints to: Anna Spada, M.D., Istituto di Scienze Endocrine Ospedale Maggiore, Istituto di Ricovero e Cura a Curattere Scientifico, Via Francesco Sforza 35, 20122 Milano, Italy. E-mail: anna.spada{at}unimi.it.

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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